ROOTING OUT REMEDIES

Plants ranging from the Pacific yew to the apparently banal potato, aubergine and tomato are being plundered by drug companies in the war against disease
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The Independent Culture
Within the infant rind of this small flower

Poison hath residence, and medicine power

- Shakespeare, 'Romeo and Juliet', II ii

It doesn't take a degree in botany to guess how the soapwort got its name. The common name for the plant Saponaria officinalis refers to its traditional use in making detergent for the textile trade. But it does take a leap of imagination to think of the same plant producing the warhead for a guided missile used to seek out and destroy cancer cells. Yet that is what is happening at Southampton General Hospital, in the first British trial of an entirely new class of anti-cancer drugs.

Saporin, a poison found in the seeds of the plant, has been stuck on to a monoclonal antibody - a protein produced by genetic engineering which locks on to a specific site on the surface of a cell. The scientists at Southampton have made an antibody lock to a site which only exists on the abnormal white blood cells that cause childhood leukaemia. When the "missile" hits its target, the saporin is absorbed into the cell where it slices up the cell's ribosomal RNA - part of the mechanism for making new proteins needed for the its survival.

This combination of plant product and biotechnology marks the birth of a third generation of herbal remedies. The first generation were the crude plant extracts used by herbal healers in all cultures since prehistory; the second appeared with the beginnings of modern chemistry, when scientist were able to identify, isolate and even modify the active components. Now all three approaches are attracting increasing attention from scientists and the pharmaceutical industry.

Descriptions of plant remedies go back as far as our earliest records. Some are still used in their natural forms. Morphine, the active constituent of opium, is still the most powerful painkiller available to doctors; drug companies find it cheaper to harvest the raw material from the plant than to make it by chemical synthesis. But morphine is an exception: a quarter of the prescription medicines in Britain today contain substances originally produced from plants, but most are now made synthetically. "By isolating and purifying the active compound," explains David Phillipson, emeritus professor of pharmacognosy at the London School of Pharmacy, "you can regulate the dose and get a more reliable medicine with fewer side-effects."

But chemists haven't found all the answers. They have yet to find synthetic compounds that are effective against common degenerative diseases such as Alzheimer's and rheumatism, or against major viral diseases such as HIV. At the same time, some mainstream drugs have become ineffective against bacteria such as the tuberculosis organism. The pharmaceutical industry is constantly struggling to keep one step ahead. The big pharmaceutical companies are desperate for new ideas, according to Phillipson. Many, like Glaxo and Sandoz, are busy checking plants which may contain compounds with therapeutic properties. Others are carrying out trials on the crude plant extracts previously thought to be at best unreliable and often unsafe. Only last month a new company, Phytopharm, was launched on the London Stock Exchange. It is testing the mixtures of different plants used in traditional Chinese medicine.

So how do industrial chemists decide which plants to look at? Glaxo and other big companies can routinely test thousands of chemicals from hundred of different plants for use against particular diseases. One way is to test each potential drug's ability to bind to receptor molecules, structures on the cell surface which enable it to interact with the outside world. There are many different types of receptors. A compound which - like the poppy derivatives - attaches to the opiate receptors on brain cells may have potential use as a painkiller, for example. But the results of random tests aren't encouraging. On average, they turn up one interesting chemical for every 16,000 tested.

Occasionally, though, these shots in the dark do hit their target. The US National Cancer Institute (NCI) plant screening programme discovered a potentially useful chemical in the bark of the Pacific yew tree (Taxus brevifolia) and began serious investigations in the 1970s. The compound, now called Taxol, was shown to be active against cancer cells; it disrupts the function of the microtubules that form the cells' internal scaffolding.

The drug was licensed to the pharmaceutical company Bristol Myers Squibb, which began the long process of clinical trials in 1983. As well as proving the clinical value of the drug, the company had to find another source for the complex molecule, which was difficult to reproduce by chemical synthesis. The Pacific yew is rare and slow-growing, and stripping the bark kills the tree. Environmentalists reckoned it would take six 100- year-old trees to produce the Taxol needed to treat one cancer patient. Eventually the problem was solved by using a semi-synthetic form produced from a renewable source, the needles of the European yew (Taxus baccata). The drug was finally licensed in the US in 1992 for treatment of ovarian cancer, and in 1995 it was also approved in Britain.

Scientists wanting to shorten the odds against finding a potential blockbuster like Taxol have two alternatives to random screening. They can ask the people still using old herbal cures, or they can look at ancient manuscripts describing herbal remedies. The first - ethnobotany - is the more promising. In a world-wide investigation of folk remedies, the American NCI discovered 10 times as many useful leads than by random screening. But the biggest range of potential plant compounds is found in the rich diversity of the tropical rain forest, and at current rates of deforestation, who is to say that the plants or the cultures that use them will still be around when the necessary tests are completed?

Rooting around in dusty libraries can also produce some useful clues. Two British research groups are studying plant compounds which may have potential uses in the treatment of Alzheimer's disease. At Newcastle University Dr Elaine Perry is trying to extract an ingredient in sage which may slow the progress of the disease. Loss of memory is the main symptom of Alzheimer's, caused by the gradual disappearance of a chemical which carries messages between brain cells, acetylcholine. She says in ancient Greece garlands of sage were worn by students during examinations to improve memory. Therefore, she was only slightly surprised to find that an extract has the same beneficial effects as the drug Tacrine - the only currently available drug for treating the condition, which maintains levels of acetylcholine in the brain but causes liver problems in some patients.

Meanwhile at Bath University, Professor Barry Potter's team is investigating a compound in delphinium seeds. The Roman writer Pliny recommended rubbing the seeds into the scalp to remove lice; the active ingredient is not only a potentially useful insecticide but attaches to the particular brain receptors affected by Alzheimer's disease. Potter hopes studies of the drugs' effects will help improve basic understanding of the condition.

Even common-or-garden plants are producing possible leads. Rob Nash of the chemistry group at the Institute of Grassland and Environmental Research in Aberystwyth, is looking at some very ordinary plants in his quest for new compounds - potatoes, aubergines, tomatoes. He is particularly interested in plants with a reputation for being effective against coughs, including those caused by TB. The plants range from blackcurrants to garlic. "What we're really looking for is anything that might lead to a drug for tuberculosis, because at the moment we have nothing to combat the drug resistant forms."

And plants with properties that have been thoroughly investigated by professional pharmacologists, and other, less serious students, are turning up some surprises. Fred Evans, Professor of Pharmacognosy at the London School of Pharmacy, is about to publish results on the use of cannabis oil pills in treating the pain of multiple sclerosis. "It is most unfortunate," he says, "that its use as a social drug has overshadowed its potential use as a medicine."At this stage he will only describe the results as "interesting" - but is looking for money to carry out larger trials.

Professor Evans's study was the first officially sanctioned experiment with cannabis in Britain, and he had to get special permission to carry out the work. For other researchers, lack of cash is a bigger hurdle than bureaucracy. At the Scottish Crops Research Institute Jock Forrest is developing lectin, a compound from daffodil bulbs which he says could be used as a treatment and vaccine for HIV. The body's antibodies recognise particular shapes or antigens on the surface of a foreign body and destroy it, and also target "key" proteins on the alien virus. Current vaccines for HIV, intended to stimulate antibody production, do not work very well - the virus is small and can change shape to evade the body's natural defences. The proposed vaccine would mimic the shape of the virus "key", but as a large molecule it would be easily recognised by the immune system, and might provoke the strong immune response necessary to protect against future infections. Forrest's team has no money to test the theory further and the big pharmaceutical companies are too busy with their own projects to buy in unconventional ideas from outside.

Yet, overall, David Phillipson is optimistic about the future for plant remedies. He is concerned, though, that people may place too much faith in their natural qualities. "There are nasty molecules in nature just as there are nasty synthetic molecules." He says that recent developments in analytical techniques will make it easier to find the active components. "Then we can make synthetic analogues that improve on nature."

Julia Durban works as a senior producer with the BBC World Service Science Unit.

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