In the 18th century, dedicated followers of fashion cheerfully powdered their noses with toxic white chemicals. ‘Pale’ was beautiful even if it did mean poisoning your nervous system with lead. In recent decades we have cheerfully sought a different poison with which to alter our complexions: ultraviolet radiation. Now the poison is exacting its toll. All over the world the three forms of skin cancer – basal-cell carcinoma, squamous-cell carcinoma and melanoma – are rocketing up the league tables of human disease. What began as a postwar fetish for sunbathing is rapidly developing into a world health crisis.
Hardest hit has been Australia, where a lethal mix of Celtic skins and subtropical latitudes has made skin cancer 10 times as prevalent as it is in northern Europe. For the first time in Queensland last year, melanoma became the commonest cancer on record, pushing cancer of the large bowel into second place and earning the ‘sunshine state’ a new and decidely less appealing title: ‘skin cancer capital of the world’. Australia’s total crop of melanomas this year will number at least 7000, and a further 140 000 people, nearly 1 per cent of the population, will acquire a basal-cell or squamous-cell carcinoma. While most of these tumours will be benign and easily removed, about one in seven cases of melanoma will prove fatal.
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What worries health officials most is that the figures for skin cancer are getting progressively worse – and not just in Australia. Certainly the incidence of melanoma there has doubled over the past decade, but there has been a similar explosion of cases in northern Europe, too. A study published last month in The Lancet, for example, reports an 82 per cent increase in melanomas in Scotland between 1979 and 1989, the latest year for which figures are available. This trend is not unusual. In most countries with predominantly white-skinned populations the incidence of melanoma is climbing by about 7 per cent per year, a rate higher than that of any other major cancer.
Why? The overwhelming consensus among epidemiologists is that the blame lies not with the thinning of the ozone layer – a problem still in its infancy – but with something more mundane: beach holidays and the myth of the healthy tan. ‘Changing habits of sun exposure’ are the fundamental problem, says Rona Mackie, an epidemiologist at the University of Glasgow who studies melanoma trends in Scotland. ‘People today have more opportunities than their grandparents to go to the Mediterranean and burn off their skin.’ Mackie adds that although ‘we have no good data on non-melanoma skin cancers in the UK, the trend is sure to be upwards’.
Researchers also agree that it will be at least five years before either the ozone ‘hole’ over Antarctica – which drifts over countries such as Chile and Australia when it breaks up at the end of spring – or the ozone losses discovered recently over the northern hemisphere begin to feed the current trend. But how marked the rise in skin cancers will be is a vexed question. Because ozone declines seasonally, and largely at the poles, predicting how much additional UV radiation is likely to reach the populated areas of the earth over the next few years is more of an art than a science. This point was reinforced last month by the results of the European Arctic Strato-spheric Ozone Experiment. Between November and March, the project detected decreases of be-tween 10 and 20 per cent in stratospheric ozone – a sharp decline, but nowhere near the 40 per cent loss predicted previously by NASA scientists.
A compounding problem is that measurements at ground level of UVB – the narrow band of sunlight between 290 and 320 nanometres that is thought to do the most biological damage – are notoriously inaccurate. Only in the southern hemisphere have scientists detected significant increases in UVB. Melbourne’s Bureau of Meterology, for example, has recorded an 8 per cent rise in average summer levels of UVB since 1980. Similar attempts to detect increases in ground-level UVB in Europe and the US have so far produced equivocal results.
Be that as it may, each new report of ozone loss has biologists frantically refining their calculations of the likely toll on human health. According to a report published last month by the United Nations Environment Programme and the World Health Organization, the damage spared by phasing out CFCs and other ozone-eating chemicals by 1996, a few years ahead of the original deadline, will in the long run lead to a million fewer cases of skin cancer and about 350 000 fewer cases of cataract-induced blindness. If the current rate of ozone depletion continues, adds the report, the ozone layer over Europe and North America will be 10 per cent thinner by the year 2000, leading to a 26 per cent increase in the incidence of non-melanoma skin cancer.
The rule of thumb is that a 1 per cent loss of ozone produces an increase of between 1 and 2 per cent in UVB, which in turn gives an increase of between 2 and 4 per cent in the incidence of non-melanoma skin cancer.
Gloomy news. Yet some researchers think the ozone crisis will have the opposite effect on human health. By jolting people into changing their behaviour and staying out of the sun, it could lead to a net reduction in skin cancer. One such researcher is Robin Marks, an Australian epidemiologist who advises the Anti-Cancer Council of Victoria on skin cancer. Living in a country which has the world’s highest levels of skin cancer, he could be forgiven for being pessimistic about ozone depletion. In fact he is optimistic.
In the mid-1980s most Australian states launched hard-hitting public education campaigns designed to encourage early detection and prevention of skin cancers. Although the campaigns have not yet curbed the rate of increase, Marks and his colleagues believe they are seeing the first signs of change in people’s behaviour. A recent telephone-based survey by the Anti-Cancer Council of Victoria reveals that people are spending less time in the sun and suffering fewer bouts of sunburn than they were before the campaigns began. Another sign of heightened public awareness is that the melanoma mortality rate in Australia is not climbing as briskly as the incidence rate. Increasingly, skin tumours are being spotted well before they become invasive.
With almost evangelical fervour, Marks warns against deliberately seeking a tan: ‘A tan is not healthy; a tan is not a sign of beauty; a tan is not a sign of higher socioeconomic status.’ In his zeal to convert he speaks of clothes as ‘personal shade zones’, extolls the virtues of densely-woven fabrics and broad-rimmed hats and notes with satisfaction that in Australia sunscreen advertisements have begun to emphasise the protective, rather than the ‘tanning’, qualities of their products – although this is still not the case in northern Europe (see illustration overleaf).
Wide-brimmed hats
This belief in the power of behavioural change is echoed elsewhere. Mackie, for example, believes that ‘very minor changes in habit such as wearing a hat with a wide brim or staying indoors in the middle of the day could dramatically reduce the incidence of skin cancer’. She draws comfort from the early results of an education campaign launched in Scotland in 1985, aimed at encouraging the early detection of melanomas. Last month, Mackie and her colleague David Hole reported in the British Medical Journal a drop of about 20 per cent in the rate of mortality from melanoma among women in Scotland – a fall that coincides with the current education campaign.
‘The predictions are assuming that people can’t change their habits,’ says Mackie, ‘but people are not stupid.’ That said, as she and Hole concede in the British Medical Journal, ‘alternative approaches seem to be needed to achieve a similar result in men.’
Others are less optimistic. ‘Think of the smoking problem,’ says Joe Scotto, an ozone specialist based at the US National Cancer Institute in Bethesda. ‘How long did it take people to change their habits?’ The rising toll of skin cancer could be a taste of things to come, he says. ‘If we are seeing a large increase in melanoma just because of lifestyle changes, think what upping the amount of incident UV radiation will bring. We may have to change our behaviour just to maintain the status quo.’
The vagaries of human behaviour aside, there is another, perhaps even more fundamental, barrier to making solid predictions about the health consequences of ozone depletion: the inherently complex, in parts almost baffling, relationship between UV radiation and melanoma. It is impossible to calculate how much exposure to UV radiation is needed to cause a melanoma.
Few epidemiologists would question the causal link between UV radiation and non-melanoma skin cancers. A host of studies have shown that these cancers correlate nicely with latitude, and by implication UV levels. The closer to the equator a white-skinned person lives, the more likely he or she is to get a basal-cell or squamous-cell carcinoma. Moreover, these carcinomas occur on the bits of the body we expose most: face, hands, arms and neck. What seems to count most is simply cumulative exposure to sunlight. People who work outdoors are especially prone to non-melanoma skin cancers.
The epidemiology of melanoma tells a more complicated story. The people most at risk, curiously, are not those who work outdoors but office workers. The favoured theory is that melanoma is somehow caused by intermittently exposing the body to relatively high doses of UV radiation. ‘It seems to be associated with acute burning experiences,’ says Mackie. This is underscored by the fact that melanoma is one of a handful of cancers that defy the traditional link between poverty and disease. For most of these, notably leukaemia and breast cancer, the reasons are obscure – but not so for melanoma: affluence and holidays in the tropics go hand in hand.
Further evidence linking melanoma to UV radiation has come from studies of a rare genetic disorder known as xeroderma pigmentosum. The disease is caused by a defect in a gene encoding an enzyme that repairs damaged DNA – not just any damaged DNA but precisely the kind formed by UV radiation, so-called ‘pyrimidine dimers’ (mutant strands of DNA that contain aberrant chemical links between adjacent pyrimidine bases). People carrying the defect are a thousand times more likely to develop melanoma than people with functional copies of the gene. A small clinical trial of a skin cream containing an enzyme that can repair pyrimidine dimers is currently under way at St Thomas’s Hospital in London.
Puzzling appearance
Other aspects of the biology of melanoma are harder to explain. One of the greatest puzzles is why melanomas appear most frequently on men’s trunks and women’s legs. If exposure to UV radiation really is the primary cause, why not the face and arms as well? Confusion also reigns over some of the molecular and cellular changes that cause skin tumours, not just melanomas but basal-cell and squamous-cell carcinomas too. How many genes must be ‘hit’ before a melanocyte (pigment cell), basal cell or squamous cell turns into a tumour cell? Is there a specific gene ‘for’ melanoma, and if so what kind of protein does it encode? Perhaps most fundamental of all, how do tumour cells in the skin manage to avoid being destroyed by the immune system?
Some clues are beginning to emerge from genetic studies , but where researchers have made most progress in recent years is in unravelling the complex immunological effects of UV radiation. Increasingly, evidence suggests that one of the main reasons white-skinned people are so susceptible to skin cancers is that UV radiation suppresses the body’s immunity to tumour cells in the skin. In effect, UV radiation delivers a double blow. Not only does it make cells cancerous by damaging their DNA, but it also dampens the very response that is needed to destroy such cells once they have formed. But what, if any, implications this dampened immune response has for our ability to resist infectious disease remains highly controversial.
‘The immune response tips the balance in favour of a tumour,’ says Mary Norval, of the University of Edinburgh. Like many researchers trying to unravel the biological effects of UV radiation, Norval points to the high incidence of skin cancers among people with AIDS as independent evidence of a special link between impaired immunity and skin tumours. Even staunch sceptics of the link between UV radiation and infectious disease concede that the immunosuppressive effects of UV light are likely to help cancerous skin cells to evade destruction.
Immunologists have long known that exposing laboratory mice to UV radiation suppresses their immune system. Mice irradiated with UVB, for example, are unable to reject tumour cells transplanted from mice with skin cancers. Such cells normally trigger a fierce immune response and are destroyed. Moreover, it has been known for years that sunlight can activate latent infections of herpes simplex virus (cold sores are more common in summer than in winter). Such observations have stoked concern over the immunological effects of ozone depletion. Will the expected increase in UVB levels impair our immunity to infectious diseases?
Epidemiologists reply with an emphatic ‘no’. There is no evidence, insist Mackie and Marks, linking exposure to sunlight to any disease other than skin cancer. If UV radiation really does cause a general suppression of the human immune system, then why does Australia, the country with the highest incidence of skin cancer, not also have an unusually high incidence of infectious disease? Marks calls immune suppression a ‘red herring’ – an interesting biological phenomenon, but one of questionable relevance to the broader debate about public health and UV radiation.
To Margaret Kripke, of the MD Anderson Cancer Center at the University of Texas, these are ‘opinions based on no information’. Like most immunologists investigating the biological effects of UV radiation, she warns against complacency. She admits that the extent to which UV exposure suppresses human immunity is uncertain, and that the phenomenon cannot possibly be involved in every infection. But she is adamant about one thing: you cannot rule out a link between UV exposure and infectious disease by relying solely on conventional epidemiology.
‘It’s not just a question of incidence,’ Kripke stresses. The effects of UV exposure are likely to be more subtle, and might include altering the duration or severity of an infection. ‘We need to determine whether exposure to UV could tip the balance of the host-defence mechanism in favour of a pathogen.’
Suppressing evidence
Advocates of a possible link between UV light and infectious diseases marshal several lines of evidence. In the late 1980s, groups in Japan, Australia and the US discovered that exposing mice to UVB radiation weakens their immune response to a number of infectious agents, including leishmania, Candida albicans (the fungus that causes thrush), mycobacteria and herpes simplex virus. At about the same time, an Australian team discovered that people who regularly use solariums exhibit weakened immunity, too. Then in 1990, researchers in the US, led by J. Wayne Streilein of the University of Miami, reported what is probably the strongest evidence so far that UV light can suppress human immune responses.
The Miami researchers exposed a group of volunteers to low doses of UVB radiation and then measured their ability to respond to an immunogenic chemical, 2,4-dinitrochlorobenzene. Usually when this chemical is painted onto skin it stimulates what immunologists call a ‘contact hypersensitivity response’, a standard measure of the responsiveness of someone’s immune cells. But 40 per cent of the Miami researchers’ subjects failed to give any such a response on patches of skin that had been exposed to the UVB light. Moreover, patients with skin cancer proved even more sensitive to UVB. In virtually all cases, the exposed patches of their skin became immunologically tolerant to 2,4-dinitrochlorobenzene.
Exactly how UVB radiation causes these effects is far from clear, however. In mice and humans, UVB destroys Langerhans cells – dendritic cells stationed in the epidermis which are believed to play a part in immune ‘surveillance’, scanning skin tissues for invading organisms. But researchers are split over what role, if any, this destruction has in immune suppression. Likewise, while a plethora of studies show that UVB light stimulates the proliferation of suppressor T cells – cells that can block immune responses to specific target cells – how it does so is a subject of intense debate and research .
Cosmetics scare
One chemical that has been linked to immune suppression is urocanic acid, the most abundant of all substances found in the outer layer of the skin. Since the mid-1980s there has been a steady flow of evidence from laboratories in the US, Australia and Britain implicating urocanic acid as the molecular trigger for at least some of the immunological effects of UVB light. In its common form urocanic acid is harmless. But exposed to sunlight, it switches to a molecular form that suppresses the immune system in mice – a finding which has proved acutely embarrassing for the cosmetics industry. For well before researchers knew of its link with immune suppression, urocanic acid was used as a moisturising agent in a whole range of skin lotions. In the 1960s, ironically, the substance had even been hailed as a ‘natural’ sunscreen.
The problem for the cosmetics industry came to a head at the end of the 1980s, when scientists in the US and Australia discovered that some companies were still using urocanic acid in their lotions, six years after the first paper on its role in immunosuppression had been published.
In 1989, Vivienne Reeve and her colleagues at the University of Sydney discovered urocanic acid in three skin creams produced by the Japanese cosmetics company Shiseido. The following year they made public results showing an unusually high rate of skin tumours in mice painted with urocanic acid and exposed to standard levels of UVB light. Amidst a blaze of publicity the Australian government asked manufacturers and retailers to withdraw products containing urocanic acid, and Shiseido complied.
In 1990 urocanic acid also came to light in moisturising lotions produced by the American cosmetics giant Estee Lauder. The discovery prompted Edward De Fabo and Frances Noonan, two dermatologists based at the George Washington University Medical School, to begin lobbying for a ban on its use in all skin lotions sold in the US. The US Food and Drug Administration is still reviewing the evidence.
Estee Lauder says that it no longer makes or sells any products containing urocanic acid. It also says that its decision to remove the ingredient from its lotions in September 1990 was ‘voluntary and not the result of pressure from any scientific body or consumer group’. De Fabo, however, remains unimpressed: ‘The fact is that they knew it could be immunosuppres-sive as far back as July 1989’. He also claims to have purchased Estee Lauder products containing urocanic acid as late as March 1991. ‘No products were withdrawn,’ admits a spokesperson for Estee Lauder. ‘There was no sense of urgency about getting product off the shelves since there was no safety issue and no regulatory body has banned its use.’
In a paper to be published later this year in the Journal of Investigative Dermatology, the Sydney researchers report that one of the suspect lotions withdrawn in Australia suppresses the contact hypersensitivity responses of hairless mice by 68 per cent. Major British manufacturers of skin lotions assured ¿ìè¶ÌÊÓƵ that they no longer use urocanic acid.
The human immune system poses another potential problem for the cosmetics industry. A long line of studies suggests that the most commonly used sunscreens may not protect against the immunosuppressive effects of UV radiation. The most recent work on mice, by Kenneth Ho and his colleagues at the University of Sydney, shows that the two most popular UVB absorbers – octyl dimethyl para-aminobenzoate (Padimate O) and 2-ethylhexyl-p-methoxycinnamate (2-EHMC) – prevent UV light from destroying Langerhans cells but fail to block immune suppression. In the early 1980s, researchers studying the effect of solariums on the human immune system revealed that Padimate-O does not prevent UV radiation suppressing the activity of natural killer cells.
Why sunscreens should fail in this respect is unclear. ‘It is possible,’ argue Ho and his colleagues, ‘that the sunscreens absorb the wavelengths of UV responsible for reducing the density of Langerhans cells, but allow transmission of sufficient energy of the wavelengths responsible for systemic immune suppression.’ One theory is that sunscreens fail because they do not prevent UV radiation from activating urocanic acid in the outer layer of skin.
All this highlights what many cancer researchers feel is a key problem with sunscreens: they give the wearer a false sense of security. ‘The message is not to get this overly confident feeling that everything is OK,’ says De Fabo. ‘It may not be protecting you against immune suppression.’ The need for caution is all the greater, he adds, because ‘most of us probably have tumour cells in our skin initiated at a young age which are being controlled by our immune systems’. Indeed, epidemiological studies suggest that one to three episodes of blistering sunburn in early childhood predisposes the victim to melanoma in later life – an indication, say some researchers, that immune suppression might well play a part in allowing cells damaged previously to turn cancerous and escape surveillance by the immune system.
Perhaps a more fundamental question is why sunlight should have such seemingly detrimental effects. Why have we not adapted to UV radiation by evolving an immune system that is innately resistant to it? Nobody knows for sure, but one idea is that a measure of immune suppression is helpful because it quells a potentially damaging reaction to sunlight. Because of their radically altered surfaces, cells damaged by sunshine look ‘foreign’ to immune cells; a degree of immune suppression may thus help to prevent sunburnt skin from being rejected. In the words of De Fabo: ‘Immunosuppression is basically a protective mechanism. It closes down an autoimmune attack on sun-damaged cells, giving them time to repair themselves.’ And that, he claims, is why it was selected for in evolution.
In fact, far from being a poor adaptation, our response to UV radiation reveals just how exquisitely attuned to our environment we really are. It is a response that extends well beyond the production of a little extra melanin to shield the lower layers of our skin, right through to the careful attenuation of a complex network of potentially damaging immune responses. The snag is that these protective mechanisms are finely tuned – so finely tuned that if stressed by too much sunbathing or the sudden disappearance of stratospheric ozone they are likely to collapse. In this, unfortunately, there is no reason to suppose we are unique. Plants, fish and plankton: all have undoubtedly evolved a similarly subtle array of protective mechanisms the effectiveness of which now hangs in the balance. Unlike us, however, they cannot retire to the shade or don a wide-brimmed hat when the effects of ozone depletion take hold. As one melanoma specialist ruefully put it, ‘when that happens, skin cancer could well prove to be the least of our problems’.
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Fishing for melanoma genes
Melanomas behave like most other human tumours. Researchers believe that they evolve through the stepwise accumulation of defects in genes that restrain cell division – oncogenes and tumour suppressor genes. Yet the quest to identify exactly which genes are critical to melanoma growth has taken molecular biologists into unchartered territory. None of the genes that have so far been linked to common cancers seems to fit the bill, although one well known oncogene, ras, appears to be mutated late in melanoma development. As a consequence, genetic screening for the traits that put people at risk of melanoma is not yet possible.
Researchers are pinning their hopes on identifying the genetic defect that causes hereditary melanoma. A collaborative venture is under way, led by Richard Kefford of the University of Sydney and David Housman of the Massachusetts Institute of Technology in the US, to identify the gene that harbours the defect.
A false alarm came in 1989 when the American team claimed to have traced the gene to chromosome 1. Research on familes in Australia and elsewhere failed to confirm the link, and attention has since switched to chromosome 6. Two factors hampering progress are the rarity of hereditary melanoma and its high mortality rate, both of which make the collection of melanoma tissue difficult.
Clues have also come from a less likely quarter – a tropical fish found in the Gulf of Mexico. Researchers have long known that one breed of the fish, a cross between the swordtail (Xiphophorus helleri) and platyfish (X. maculatus) is genetically predisposed to melanoma. More recently they have discovered why: it carries an oncogene called X-mrk which, when not held in check by a specific tumour suppressor gene, transforms its pigment cells into rapidly dividing tumour cells. In 1989, the fish oncogene was cloned by researchers in Germany who discovered that it encodes a receptor molecule with a structure similar to that of a protein found in mammals, the epidermal growth factor receptor. Researchers believe that a protein belonging to the same family as this receptor, may play an important part in the development of human melanomasFishing for melanoma genes
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2: What sunlight does to your immune system
UV radiation appears to trigger two quite distinct immunological effects. One is confined to the patches of skin that are actually irradiated; the other develops in the immune system as a whole. This second, so-called systemic, effect accounts for the fact that an irradiated mouse will accept skin tumour transplants anywhere on its body – even on patches of unexposed skin.
The cellular events underlying these immune responses are uncertain, although both seem to involve the release of suppressor T cells from the lymph nodes. The scientific debate has revolved around two questions: what part does the destruction of Langerhans cells in the epidermis play in immune suppression, and how does UV radiation stimulate the lymph nodes to release suppressor T cells?
Everyone agrees that the second event requires one or more biochemical messengers to carry a signal from the skin to the lymph nodes. But the identities of these messengers are a mystery. When irradiated with UV light cultured skin cells release a shower of different cytokine proteins when irradiated with UV light, any one of which may in theory signal the immune system. According to Margaret Kripke, of the University of Texas, recent studies implicate two cytokines, interleukin-10 and TNF-alpha.
When it comes to the role of Langerhans cells the scientific consensus collapses. At first glance, their destruction would seem a likely cause of immune suppression. When an infectious agent invades skin tissue, Langerhans cells pick up some of its protein fragments and carry them to the lymph nodes, which respond by despatching killer T cells specific for the pathogen. But critics point to two snags. First not all mice and humans who lose Langerhans cells through being exposed to UV light acquire suppressed immunity. Secondly, sunlight suppresses the immune systems of blacks and whites, suggesting that melanin – the protective pigment that lies well above Langerhans cells – is no safeguard against the immunological effects of UV light.
Equally controversial is the identity of the photoreceptor molecule which initially absorbs UV radiation in the skin. Opinion is firmly divided over whether it is DNA or a substance known as urocanic acid.
Kripke believes that immune suppression begins when DNA inside cells in the skin absorbs UVB light, and as a consequence turns on a host of normally resting genes. She and others have endeavoured to prove this theory with research on an unlikely laboratory animal: the South American opossum (Monodelphis domestica).
What makes this creature so attractive to photobiologists is that, unlike rodents, it possesses a DNA-repair enzyme that is activated by visible light and which can heal genetic damage caused by UVB radiation. Kripke and her colleagues found that a single dose of radiation – sufficient to damage DNA belonging to Langerhans cells but not to activate the repair enzyme – led to immune suppression in the opossum, but that UV light followed by a dose of visible light did not. By stimulating DNA repair, it seemed, they had blocked the immunological effects of UV light. More recently, the researchers have replicated this result on mice impregnated with tiny biochemical packages, or liposomes, containing a DNA-repair enzyme.
A rival theory holds that the initial event in immune suppression is UVB absorption by urocanic acid, the most abundant substance found in the outer layer of the skin. Urocanic acid was first suggested as a likely accomplice of UV light in the early 1980s by Edward De Fabo and Francis Noonan, of the George Washington University in Washington, DC. The researchers found that urocanic acid switches from a trans to cis geometry at exactly the wavelength which triggers immune suppression. ‘When it absorbs a photon the molecule bends,’ says De Fabo, ‘and when that happens it becomes immunologically active.’
Later, researchers discovered that they could mimic some of the immunosuppressive effects of UV light simply by painting cis-urocanic acid onto the skins of mice. Treated in this way, the mice exhibited both local and systemic immune deficiencies. Most important of all, they produced suppressor T cells in profusion.
Researchers are now trying to solve the puzzle of how urocanic acid stimulates the production of suppressor T cells. At the University of Edinburgh, Mary Norval and her colleagues have uncovered evidence that it may act on Langerhans cells, hampering their ability to recruit killer T cells in the lymph nodes.
Another piece in the jigsaw has come from Reeve and her colleagues in Sydney. Using urocanic acid tagged with a radio-active marker, they have found that it is not restricted to the tissues of the skin: it can migrate to the lymph nodes. Reeve and Norval believe that urocanic acid might mediate its effects on the immune system by stimulating histamine receptors.
‘UV radiation clearly has multiple effects on the immune system,’ says Norval. ‘Cis-urocanic acid is not the whole story, but it is certainly an important part of it.’ De Fabo is more forthright. ‘For the first time,’ he says, ‘we have shown that there is a receptor on the surface of skin which is able to mediate the immunological effects of sunlight.’ He cites with enthusiasm experiments showing that mice fed on a diet rich in histidine – the amino acid from which urocanic acid is formed in the skin – are more susceptible to the immunosuppressive effects of UV light.
