The season of consumerist indoctrination, dietary excess and Panglossian sentimentality is approaching its peak, so here is a heart-warming little Christmas story. Actually, its roots – literal and metaphorical – go back well before the intrauterine innovations that traditionally attended the conception and birth of Christianity’s founder and it will warm principally and selectively the hearts of cheerful cynics and pessimists like myself (and, I assume, like many readers of B and W) in whom any habits of optimism have long been replaced by a null hypothesis as the default mode. One of the favourite hobbies of People Like Us is saying ‘I told you so’ and we derive additional schadenfreude from noting that even in the current financial crisis, it is a hobby that no government has yet got round to taxing. This is a story about mistletoe and its alleged ability to cure cancers.

Like most doctors, especially those with an interest in medical history, I have never had anything against plants or herbs. They have provided us with many useful therapeutic agents and will doubtless provide quite a few more. However, I reject the notion that just because something is herbal, it must be effective, along with the allied notions that herbs are harmless and that the more exotic the plant, the greater the efficacy. In short, I am all for plant science as opposed to plant magic. I am also a great fan and was sometimes a deliberate employer of the placebo effect in the days when doctors were allowed to use it but I maintain that the function of placebos is primarily – and for entirely benevolent purposes – to deceive patients, not those who are treating them. Deprived of this now-forbidden, politically incorrect experience, even proper doctors who do respect proper evidence usually have little awareness of just how powerful the placebo effect can be and are regularly surprised by it. ‘Alternative’ practitioners, as a rule, simply don’t want to know about it.

Mistletoe is an obvious candidate for plant magic, deeply embedded as it is in our folk history and potentiated by its association with Druidic mysteries on the one hand and Yuletide lechery on the other. Perhaps because it is itself a kind of ‘growth’ on a tree, mistletoe extracts have been used and recommended for the treatment of cancer. As usual, enthusiasm for mistletoe by its advocates is inversely proportional to the amount of evidence for its effectiveness, but it is a characteristic of ‘alternative’ practitioners that they don’t let anything as boring as evidence get in the way of a rattling good bit of myth or symbolism.

Of course, it’s entirely possible – in principle – that mistletoe contains a hitherto unrecognised anti-cancer drug of amazing potency and few side-effects. However, the null hypothesis requires us to start from the presumption that it doesn’t – that it has no beneficial effects at all and requires researchers to disprove that presumption, though I suspect that most alternative practitioners wouldn’t recognise a null hypothesis if they were strangled with one. As always, only a clinical trial fairly comparing like with like can tell us whether the enthusiasm of its advocates is justified. (As one of our better Prime Ministers noted, “Considering that enthusiasm moves the world, it is a pity that so few enthusiasts can be trusted to tell the truth”.)

About ten years ago, I was visiting a medical friend and colleague in Berlin, where we had been organising a conference. Sitting in her office while she dealt with some patients on the wards, I flicked through a few of the mainly German medical journals on her desk. My German is on the rudimentary side (apart from the texts of Schubert lieder¸ which are of limited relevance to medical science), but most foreign-language journals helpfully provide an abstract in English and a lot of medical German is encouragingly similar to medical English. My Berlin friend kindly translated the bits that I couldn’t understand. That is how I became aware of an important randomised multi-centre study[1] of mistletoe extract involving 495 patients that had recently taken place in Germany, where mistletoe seemed to be popular. This popularity may owe something to the fact that in a fee-per-item medical system, as in Germany, treatments requiring frequent injections are nice little earners for the doctors who prescribe them.

The important thing about this particular study, and one that makes it relatively easy to understand and interpret even for non-medical readers, is that all the patients were suffering from squamous cell carcinomas of the head and neck. You don’t need to know in detail what a squamous cell carcinoma is. All you need to know is that it is a type of cancer arising mainly in the skin of the head and neck region or in the mucous membranes lining the mouth, nose and throat. From the researchers’ point of view, this has the advantage that such tumours are much easier to observe and assess than cancers affecting internal organs. They can be seen, measured and often felt directly or with one of those circular, head-mounted mirrors that cartoonists are so fond of depicting. They do not need special techniques like x-rays, CT or MRI scans or investigations that require a mini-camera attached to an endoscopic tube to be swallowed or inserted.

After their cancers had been diagnosed, histologically (ie microscopically) confirmed, and treated with surgery alone or surgery plus radiotherapy as deemed appropriate by conventional treatment standards, the patients were randomised to either twice-weekly subcutaneous injections of mistletoe extract for four three-month cycles separated by four weeks, or to no mistletoe. Understandably, since injections hurt, no placebo injections were given and therefore the study was not ‘blinded’. (That is, both the patients and the doctors knew whether or not mistletoe had been administered and might have been biased by this knowledge.) However, since largely objective outcome criteria were used, this is arguably not crucial. After all, you can hardly get any more objective and less subjective in the assessment of outcomes than death vs survival, and if bias from the placebo effects were important, one would expect it to favour the mistletoe group, especially since injected placebos are usually more effective than oral ones. Patients were followed up for a median period of 40 months and this is what the researchers found: “No statistically significant differences in disease-free survival, overall survival, immune system markers or quality of life could be detected”.

I wrote about his study in ‘HealthWatch’, a newsletter published by and for clinicians, researchers and journalists committed to evidence-based medicine, whether mainstream or ‘alternative’, and it appeared in 2002. I mentioned that one reason for writing the article was that “the ineffectiveness of mistletoe is unlikely to be headline news in the journals of the alternative medicine movement. They remind me of the people who wanted to publish a newspaper which contained only good news. They also remind me of the sort of people – rather numerous, now I come to think of it – who are happy to praise their particular deity when someone recovers from a serious illness or when there is a plentiful harvest but are oddly reluctant to curse him when someone dies or when famine and earthquakes devastate the land. For many people, alternative medicine clearly is a kind of religion but its benevolent deities reside in plants, meridians or homoeopathically diluted molecules, rather than in more theologically conventional abodes. Unfortunately, to paraphrase the Duke of Wellington, if you can believe in a benevolent deity, you can believe in anything. And you may have to, if the delusion is to be preserved intact.”[2]

I was correct in my prediction. Several years later, the saintly Dr Ben Goldacre wrote something along the same lines because mistletoe was still being promoted as an anti-cancer drug. The equally saintly Dr. Edzard Ernst, professor of Complementary Medicine at Exeter University, wrote an equally dismissive editorial for the 2006 Christmas edition (Ho! Ho! Ho!) of the British Medical Journal. Yet, unsurprisingly, mistletoe is still is being promoted. It still lacks a respectable, high-quality evidence base. As a harmless, if over-priced decoration and fine old fertility symbol from pre-Roman Britain and beyond, mistletoe has an honourable place. As a specifically effective treatment for serious and still quite often lethal and treatment-resistant malignant tumours, it has no place at all – except the one we are assured it has by the magicians, witch-doctors, ideologues, perennial optimists, self-deluding fools, money-grubbers and downright charlatans who largely, though not entirely, constitute the ‘Complementary and Alternative Medicine’ movement. Some of them appear to be spiritual descendants of the great Dr Pangloss himself. Voltaire, the creator of Pangloss, had a phrase for people like that who are slaves to ideology. Écrasez l’infame!

December 23 2008

REFERENCES

1. Steuer-Vogt M, Bonkowsky V, Scholz M, Arnold W. Plattenepithelkarzinome des Kopf-Hals-Bereichs. Mistellectin-1-normierte viscumtherapie. [ML-1 standardised misteltoe treatment in patients with head and neck squamous cell carcinoma.] Arzteblatt, 46, 16 Nov, 2585-7, 2001.

2. Brewer C. Mistletoe has failed the cancer test, but you might never have known it. HealthWatch Issue 46, July 2002.