Remedy inside the test tubers

January 21, 2000

Scientists are going back to nature to search for new drugs. Geoff Watts discovers yet more things to make with a potato.

Chemists can now synthesise new molecules or refashion existing ones with an ease and speed that was once unimaginable.

Anyone who continues investigating plants in search of novel drugs is therefore apt to be written off as seriously behind the times.

But plant chemist Robert Nash, head of chemistry at the Institute of Grassland and Environmental Research in Aberystwyth, would disagree with their pessimism,

This is not really surprising

considering that he is also the research director of a company set up to look for undiscovered chemical compounds in plants.

In a further flouting of conventional wisdom, Dr Nash and his colleagues do not go tramping through the tropical rainforests in search of fresh material. "Using modern analytical techniques it has become apparent that we know surprisingly little about common British plants, even food plants.

"We recently found some new alkaloids in potatoes, for example. If you can find new compounds in potatoes, you can find new compounds in almost any plant you look at."

His choice of plants to study is not altogether random; old herbal remedies feature on Dr Nash's hit list. Dandelions, for example, were once in common use for the treatment of tuberculosis; they may contain something potentially valuable in tackling the problem posed by the re-emergence of this disease.

"We have a particular interest in compounds that affect the formation of cell walls in the mycobacterium that causes TB," says Dr Nash. "We are looking at compounds that interfere with the incorporation of a sugar called rhamnose into their cell walls. Humans do not use rhamnose at all, so something that interferes specifically with a process used by TB organisms might be a good way of attacking them specifically."

Any lingering suspicion that searching for new compounds in plant material is somehow backward-looking or sentimental vanishes when you consider the powerful techniques used by Dr Nash and his colleagues.

Developments in high-pressure liquid chromatography, mass spectrometry and other such methods allow them to produce what amounts to a unique fingerprint for any particular compound.

Searches of this kind are more sensitive and more discriminating than ever. "In the past you would not have been able to trace a lot of the compounds we now detect," Dr Nash claims.

And, far from sentimental, his logic has a sharp commercial ring to it: why do for yourself what plants already do well, and for free?

"Plants are extremely good chemists. They make a wide range of compounds that chemists still find difficult to produce. And they also make complicated molecules that may never be economical for chemists to synthesise. Taxol (a drug derived from the yew tree, and used to treat breast cancer) can be synthesised, but it is very expensive to do so," Dr Nash says.

Moreover, the kinds of chemicals most likely to be produced by plants stand an above average chance of being interesting to the drugs industry. Dr Nash explains: "Because of natural selection, a plant that produces a new compound is likely to retain it if it gives the plant an advantage in terms of, say, reducing attacks by slugs or sheep or whatever. So a lot of the compounds made by plants have been selected precisely because they are biologically active."

Molecular Nature Ltd, the company of which Dr Nash is research director, grew out of work already in progress at IGER.

Another firm, called Xenova Discovery, had commissioned the institute to extract and identify novel compounds from non-tropical plants. Xenova's investment in IGER included extra equipment and staff - but the project was short-lived because the company decided soon afterwards to

pull out of this kind of discovery work.

IGER was left with the new equipment, plus a knowledgeable and enthusiastic staff. It saw the opportunity, and took it. Molecular Nature Ltd formally came in to existence in June and, because staff and facilities were already in place, it was able to start functioning from day one.

"Xenova had been interested only in compounds for pharmaceutical use," says Dr Nash. "What had become apparent to us was that these materials have a much wider significance: to people developing new pesticides, for example." As a consequence, Molecular Nature has set out to expand its range of potential customers.

Although Dr Nash admits having had to scale a steep learning curve, an organisation such as IGER is accustomed to dealing with industry and understands the commercial imperative.

Dr Nash himself continues to spend half his time as IGER's head of chemistry, a position that allows him to make direct comparisons between the commercial and academic worlds.

"As a researcher you get used to going to scientific meetings where the audience is interested in the details of the research.

"In the commercial world the details are of less interest than the end product.

"Trying to get a new piece of equipment off the research councils can be a hard task. In general, if you have got a sound commercial case, the time actually spent putting the case to investors is less than it takes going through research councils. But you do have to make a good case for it.

"There are benefits to working in a commercial environment. But it puts more pressure on you to come up with the goods."

And a man who sees bluebells as a source of dozens of new and biologically active alkaloids demands to be believed.

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