Finding New Drugs.

There are currently over 6000 different kinds of medicine avaliable in the UK. But new drugs are needed becuase:

• new diseases are emerging
• there are still many diseases for which there are no effective treatments
• some antibiotics treatments are becoming less effective - the microorganisms that cause disease continue to evolve. As soon as we start to use a new drug, it acts as a selection pressure. Any strains of microoragnisms that are less susceptible to, or are resistant to, the drug will be at a selective advantage. These resistant organisms are more likely to survive and reproduce, and the next generation will be more resistant.

By accident: the accidental discovery of penicillan by Alexander Fleming is well documented. Most antibiotics currently in use are made by the bacterium Streptomyces. The antibiotics neomycin, chloramphenicol and streptomycin are all made from Streptomyces. But streptomycin is now rarely used, as most bacteria are resistant to it. The important antifungal drug Nystatin is derived from Streptomyces noursei.

Traditional medicine: many drugs have been used for centuries. The World Health Organisation calculates that 80% of the world's population relies on traditional medicines. In India 7000 different plants are used for their medicine properties, and in China they use about 5000 different plants. In Europe, too, some of our modern drugs have their origins in traditional medicine.

Anaesthetics: the sap of unripe poppies was used in Neolithic times in parts of southern Europe and Egypt. In the twelfth century opium from poppies was used as an anaesthetic and by the nineteenth century morphine and opium were being used. These opiate drugs reduce the nervous actions in the central nervous system. If the nerves cannot carry impulses, no pain is felt.

Observation of wildlife: there are many examples of animals self-medicating. For example:

• monkeys, bears and other animals rub citrus oil on their coats as insecticides and antiseptics to prevent insect bites and infection
• chimpanzees swallow leaves folded in a particular way to remove parasites from their digestive tract
• elephants roam miles to find clay to counteract dietary toxins
• birds line their nests with medicinal leaves to protect chicks from blood-sucking mites

Modern research: scientists have used traditional plant medicines and animal behaviour as a starting point in their search for new drugs. Research into the plants used allows them to isolate the active ingredient.

Hippocrates (a physician in ancient Greece) used an extract from willow bark to relieve pain and fever. Throughout the Middle Ages a similar extract was used n Britain. It was not until 1828 that Johann Buchner extracted the active ingredient salicin. This could be used to relieve pain, but caused stomach bleeding as a side effect. In 1897 a way was found to reduce the side effects by adding an acetyl group to salicin. By 1971 further research had revealed that salicin works by inhibiting enzymes involved in the synthesis of prostaglandins. Prostaglandins are hormone-like substancesthat have a variety of roles in cell communication. Further research has revealed other drugs that have the same effect.

Natural Medicines: in recent decades, discovery of natural drugs has concentrated on tropical plants. Owing to their great diversity, there are hopes that there may be many new medicinal drugs to discover. But it is important to remember that there may be many potential uses of wild and cultivated plants in the UK. New chemical fingerprinting technology is enabling scientists to screen natural chemicals more effectively for their activity as potential medicines.

Further research: most antibiotics developed over the past 50 years come from the bacterium Streptomyces. Biologists hope to learn how the bacterium produces antibiotics by finding out what it's genes do. They can use this information to improve current productions methods.

Pharmaceutical companies have been conducting research into the way that microorganisms cause disease. Many make use receptors on plasma membranes (cell surface membranes). If the receptor site can be blocked by a drug, then the disease-causing pathogen cannot gain access to the cell. For example, the HIV virus uses a receptor called the CD4 receptor. The CD4 receptor can be isolated and sequenced.

Once the amino acid sequence is known, molecular modelling can be used to determine the shape of the receptor. The next step is to find a drug that could block that receptor without causing major side effects.

This technology can be taken a step further by sequencing the genes that code for the CD4 receptor or for other receptors. Once this technology is developed, it may be possible to compare the DNA of a person with that of a plant or microorganism. This could identify potential medicinal drugs from the DNA. This is known as genomics. It also has potential uses in vaccines - by sequencing the genes of microorganisms, we should find a range of candidates from which vaccines can be made.