An account of the likely incidence of porphyria in European royal families. The authors are a historian (John C.G. Röhl) and two geneticists (Martin Warren and David Hunt); perhaps the book could have benefited from fewer authors but more editors. The issue of porphyria in royalty first came up with a 1966 paper in the British Medical Journal by Ida Macalpine and her son Richard Hunter, theorizing that the notorious “madness” of King George III that precipitated the Regency Crisis was porphyria. The theory has now so permeated historical consciousness that I never realized it was (and to a certain extent, still is) controversial; but at the time it most definitely was. The prevailing theory in 1966 was Freudian; George III was suffering from “sexual frustration” resulting in his rejection of Queen Charlotte and sexual attacks on Lady Pembroke (he couldn’t have been that frustrated, as he had 15 children with the Queen). The critics noted neither Macalpine or Hunter were experts on porphyria (they were both psychiatrists) and they weren’t proper Britishers (Macalpine had changed her name from Hirschmann in gratitude for refuge after her escape from Nazi Germany; the authors of Purple Secret mention her Jewishness several times, perhaps hinting that her critics were anti-Semitic). Critics also claimed George III’s reported symptoms were vague enough to be consistent with an assortment of diseases in addition to porphyria, and that if it was genetic porphyria half of his children should have had it as well.


Macalpine, Hunter and collaborator Claude Rimington attempted to answer the objections by tracking down the descendants of George III and asking them for stool and urine samples; they seemed genuinely surprised at the vehement negative responses they received. It was before the days of DNA analyses, and the genetics of porphyria hadn’t been worked out, so samples from an active case were the only way to make a positive diagnosis. The best they could do was claim that at least two people, disguised as “Patient A” and “Patient B”, had clinical signs of porphyria and were descendants of George III.


Unfortunately, the book bogs down at this point. Perhaps historian Röhl took over the writing; but what follows is page after page after page of medical records from various famous (Queen Victoria) and obscure (Princess Feodora) European royalty. While there’s an amazing amount of research involved – pages of doctor’s notes – it really doesn’t say very much. The problem is that the symptoms of porphyria are so varied that practically any complaint can be associated with it (headache, abdominal pains, constipation, “fragile” skin, light sensitivity, mental disorder, delirium, and neurological complaints). Even the sign generally considered definitive – red to purple urine – only occurs in active cases and can be caused by other illnesses – or even by eating beets. If anything, you could make the case that a lot of royalty suffered from overdoctoring and polypharmia – patients were dosed with laxatives, emetics, opiates, arsenic, antimony, brandy; prescribed diets (one princess was instructed to eat nothing but asparagus and mashed potatoes) and subjected to the dubious procedures popular at the time (bleeding, cupping, leeches and electric shocks) – often simultaneously. While some of the original complaints could well be porphyria, once the doctors got ahold of things it’s impossible to distinguish porphyria from reactions to the treatments. What the authors should have done first is provide a detailed explanation of porphyria rather than diving into the symptoms of dozens of European royals; I suspect the editors vetoed that as “too technical” and, unfortunately, it’s relegated to an appendix. Porphyria is caused by metabolic errors in the production of haem (which was originally called porphyrin, hence the name). However, the disease isn’t caused by haem deficiency, but by accumulation of byproducts from incorrect haem synthesis. Haem production is a seven-step process and can go wrong on any step; explaining the wide variety of “porphyria” symptoms and signs; each is caused by accumulation of different metabolites. The full sequence wasn’t worked out until 1995, long after the 1965 BMJ paper. (This might explain some of the criticisms of Macalpine and Hunter; many of the world’s porphyria cases occur in South Africa, where they can be traced back to the 1688 marriage of Gerrit Jansz to Ariaantje Jacobs. The South Africa doctors dismissed Macalpine and Hunter’s claim because George III’s symptoms were mostly different from those seen in South Africa. However, when it was shown that “porphyria” is a suite of conditions caused by different metabolic errors, one of the most prominent South African critics reversed his position and allowed that George III could have had one of the porphyria variants).


More or less definitive results do finally come, but are almost anticlimactic. Warren and Hunt obtain permission to sample the blood-stained shirt of Charles I and to exhume the bodies of two of Queen Victoria’s descendants – her granddaughter Princess Charlotte of Prussia and her great-granddaughter Princess Feodora. Unfortunately only one of these was a hit – Charles I’s shirt had been handled so many times that the evidence was equivocal and Princess Feodora’s grave in Poland had been robbed on several occasions and the scattered bones remaining didn’t seem to be hers. However, Princess Charlotte’s rest had been undisturbed until Warren and Hunt got to her; there was a water-damage hole in the coffin, they were able to get a fiber optics probe inside, and remotely grappled and extracted the Princess’s femur and a couple of finger bones. Amplification by PCR showed Princess Charlotte had a mutation that affected the gene that codes for protoporphyrinogen oxidase (which controls the transition from step 5 to step 6 in haem production). The princess’s medical records did show some porphyria symptoms; interestingly, one she shared with George III was a sort of sexual dementia; George III was notorious for making improper advances to Lady Pembroke during his mental episodes and Charlotte was notorious for doing the same with just about anybody.


Thus, despite a lot of interesting anecdotes about royal medical problems Purple Secret only slightly strengthens the case for porphyria in George III (George III was Princess Charlotte’s great-grand uncle). The definitive answer, of course, would involve getting DNA samples from some of the living royals and/or some of the other royal burials; the British royal family has never allowed anything of the sort (even, for example, to solve the “Princes in the Tower” mystery) and the authors of Purple Secret don’t even suggest it. ( )