SCIENCE: MOLECULE OF THE MONTH Kissing goodbye to cancer?

A toxic chemical in mistletoe is being used to combat disease. John Emsley reports

Kissing under the mistletoe is a custom dating back to pagan times, when the plant was associated with fertility and a kiss beneath it was supposed to lead to marriage and babies. But mistletoe must be hung beyond the reach of children as its berries are poisonous. The toxic chemical they contain has only just been fully analysed, yet it is already in use as an anti-cancer agent in Germany.

Mistletoe is a partially parasitic plant growing mainly on apple trees, poplars, willows and hawthorns. It is not entirely parasitic as it produces chlorophyll and is able to use sunlight to make some of its own food, although it draws water and other essential nutrients from the host tree. The main variety in Europe is Viscum album, one of around 1,300 species worldwide. Some species are parasitic on other mistletoes.

It is rare to find mistletoe growing on oak, and when it did, the druids treated it with special reverence, because this tree was sacred. Pliny the Elder in his Natural History, published in AD77, noted that the druids would cut the plant down with a golden sickle and catch it on a white mantle. Sometimes the plant was associated with ritual murder, such as that of the young man whose naked body was found in 1984 in the peat bog at Lindow Moss, Cheshire. Before he was killed, 2,300 years ago, he had eaten mistletoe.

There are two main families of mistletoe, distinguished by their white or red berries. The white ones are significantly more toxic. They are not life-threatening, but eating them causes stomach cramps and diarrhoea. Poisonous Plants and Fungi, a guide published by the Ministry of Agriculture, Fisheries and Food, recommends induced vomiting as first aid for someone who has eaten the berries.

Despite its toxicity, earlier generations used mistletoe in medicine: the juice of the berries was smeared on an affected part of the body as relief for strains, sores, impetigo, dandruff, warts and ringworm; an infusion was drunk as a medicine for epilepsy, colds, fevers, syphilis, gout and worms. It was considered particularly potent against infertility in humans and cattle.

Research earlier this century showed that mistletoe extracts acted as a diuretic, reduced blood pressure, and are an anti-spasmodic agent. At the Madaus pharmaceutical company in Cologne, Germany, the head of research, Professor Hans Lentzen, is directing a project to develop mistletoe lectin, which is already being given to cancer patients undergoing chemotherapy and radiation treatment.

Dr Uwe Pfuller, of the medical faculty of the University of Witten-Herdecke, says: "The main effects are a higher quality of life and its prolongation, and there is tumour regression. Mistletoe lectin not only kills cancer cells, but it also appears to stimulate the immunosystem."

Mistletoe lectin is the active toxic chemical, and this autumn, after six years of work, its structure was finally solved by Dr Rex Palmer and Edel Sweeney, crystallographers at Birkbeck College, London. At the Central Laboratory of the Research Councils at Daresbury, Cheshire, they bombarded lectin crystals with X-rays generated by electrons travelling close to the speed of light. In doing so, they discovered that the toxin consists of two pairs of large proteins, each pair made up of a sugar-binding part (which can attach itself to cells walls) and an enzyme part. It is the latter which wreaks havoc in the cell, by preventing essential proteins from being made.

Researchers are trying to find ways to make mistletoe lectin more effective by attaching the toxic enzyme to an antibody that seeks out cancer cells, which it can then destroy. It might also be used to control white blood cells in order to prevent the rejection of organ transplants. "We can now genetically engineer mistletoe lectin and we plan to modify its two parts to make the binding part more effective," says Dr Palmer.

The author is science writer in residence at Imperial College, London.