Links between occupational hazards and cancer
Percival Potts has entered epidemiological folk lore for providing one of the first links between occupational exposures and specific cancers… namely, scrotal cancer in chimney sweeps. And, to be clear, this was squamous cell carcinoma of the scrotal skin, not testicular cancer. And what was both striking and shocking about his observations was the young age of many the patients.
The problem has a long history. Chimney sweeps were plying their trade in Shakespeare’s day. ‘To look like her are chimney sweepers black’ he wrote in Love’s Labour’s Lost.
Correct diagnosis for cancers
But it was the introduction of tall, narrow chimneys, a response to the great fire of London in 1665, which proved a turning point. Unfortunately these stacks were prone to clogging up with soot: the chimney sweep trade took an upturn. Young boys were co-opted to do the dirty work and a consequence for them was a legacy of ill health – pulmonary disease, dermatitis, skin warts (known in the trade as soot wart), and scrotal skin cancer.
Except that, before Pott’s scrotal scrutiny, the cancerous growths were thought to be venereal and best treated with mercurials. He provided not only a correct diagnosis but a good deal of sympathy for his young patients.
Hence Sir Percy’s lament: ‘The fate of these people seems singularly hard; in their infancy they are most frequently treated with great brutality, and almost starved with cold and hunger; they are thrust up narrow, and sometimes hot, chimnies (sic) where they are bruised and almost suffocated: and when they get to puberty, become particularly liable to a most noisome, painful and fatal disease.’
A peculiarly English disease
This cancer continued through the 19th century and was recognised by surgeons and sweeps alike as a token of the trade. But then here was an anomaly. Scrotal skin cancer appeared to be a peculiarly English disease. Sir Henry Butlin, also at Barts, sent assistants tramping all over the fire stacks of Europe to Germany, Holland, Belgium and France to look for clues as to how foreigners escaped the sooty penalty.
And the answer? Well for the Germans it was obvious. They were much better organised, washed more regularly and wore protective clothing. And looked cool dudes too. But when it came to the French, Butlin didn’t hold back, confidently proclaiming it couldn’t possibly be just cleanliness ‘which is wholly inconceivable to any person who is acquainted with the general habits of French lower classes’.
Other variables Butlin thought important were the structure of fire stacks and amounts of soot plus the use, in England, of so called hard coal whereas in elsewhere in Europe coke, wood and charcoal were used, producing less sooty residue.
The link between soot and skin cancer
Which leads us to the question: what is it in soot that causes skin cancer? That will take us to the early days of the ICR in its labs in Chelsea – but before we get there, here is another conundrum. Given that chimney sweeps, even in my youth, were covered in soot all over, why was the scrotum the hot spot for cancer?
During the late 19th century it began to emerge that there were associations between occupational exposure to shale oils, pitch and tar with skin cancer, including scrotal cancer. There was clearly something very dodgy about carboniferous combustion. In 1922, a review of 141 men in Manchester with scrotal skin cancer made the surprising finding that only one was a sweep but 69 worked spinning machines or mules in the Lancashire cotton industry. Only males had this job and many started as young as eight years of age. The mules were lubricated with unrefined oil and the workers, lightly clad in cotton trousers in hot environments, leaning against the mules became encrusted in oil ‘between the upper thighs and abdomen’. And in that cavalier English way, there were no washing facilities.
Why scrotal cancer?
Now we are getting closer. Time to call on Archibald Leitch, Director of the Research Institute of the Royal Cancer Hospital in Chelsea, aka the ICR. He had calculated the risks of sweeps or mule workers dying of scrotal cancer at 1 in 1,400 and 1 in 2,000 per year respectively. But why the scrotum? Leitch suggested it was a combination of warmth and the solvent properties of sebaceous gland secretion making the skin there more absorbent and vulnerable to whatever nasty chemicals were in soot, oils and tar. I’ll buy that as an answer.
The discovery of benzo(a)pyrene
So where does this trail of sooty tar lead us? Well, actually, into 20th century cancer experimental sciences and the first mechanistic insights into cancer. Leitch’s successors and the first denizens of the ICR’s labs in Chelsea were organic chemists and their lead came from Japanese scientists – who, in 1915, induced skin cancer on rabbits’ ears by painting on coal tar. That provided an assay for asking the question: what is it in soot and tar that causes skin cancer? The answer provided by Ernest Kennaway and his colleagues at ICR in the early 1930s was a class of chemicals called polycyclic aromatic hydrocarbons, or PAHs, of which one, benzo(a)pyrene was especially potent. Which in turn led some 30 years later to the landmark discovery of Peter Brookes and Philip Lawley at the ICR that PAHs like benzo(a) pyrene caused cancer by directly binding to, and mutating, DNA.
It could, and maybe should, have been even more of an eye opener. Kennaway and colleagues, observing that cigarette tar would contain benzo(a) pyrene, asked whether this might explain lung cancer, which was beginning to escalate in incidence in the 1930s. Here’s the odd thing; nobody seems to have noticed. When Richard Doll began his landmark epidemiological studies on lung cancer in the 1950s I very much doubt he had heard of benzo(a) pyrene; he suspected motor car exhaust fumes were the cause of lung cancer. That’s not to diminish Doll’s achievements but it illustrates how opportunities can be easily missed. But then why didn’t ICR scientists run with that idea?
The trail of soot
Fast forward to the 21st century and genomic sequencing reveals distinctive signatures in cancer cell DNA of chemical carcinogens like benzo(a) pyrene. The case for cause is closed. The trail of soot is however largely forgotten. But we owe a debt to Percival Potts and his successors including Archibald.
And let’s all hope Santa is wearing extra thick pants this Christmas.
NOTE Part of the above piece was abstracted from my book ‘Cancer the evolutionary legacy’. Oxford University Press 2000.
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