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Free Radical: A Revolution In Bio-Medical Science
Jul 1, 1995

Every few years the scientific community is shaken by a new theory. Theories are put forward in every field of science from mechanics to molecules. These continual changes in scientific understanding force us to ask how much we really know about the world.

The field of medicine, as one of the oldest fields of scientific inquiry, has been particularly rich in examples of changing theories. Aristotle (384-322 BC) thought that the brain was a device used for cooling the blood. By contrast his teacher Plato (427-347 BC) had thought that it was the 'originating power of the perceptions...' Yet today scientists accept Plato's older theory. In the 1800s the state of the art brain science was phrenology, attributing certain aspects of human character to bumps and ridges on the skull. This is frowned upon today as mumbo-jumbo. However, it must be remembered that at the time it was considered as a hard and fast observational science. It was not until 1861 that Paul Broca refuted this 'science' by attributing language to a certain region of the brain, since referred to as Broca's area. Even so, phrenology continued to have its adherents and practitioners until the early 20th century. Many of the current theories of thought, emotion, psychology and psychiatry are based on observations only slightly more reliable than those made by the phrenologists. The tools used are more expensive (e.g. CT, M RI and PET scanners) but the basic approach is comparable to that of the phrenologists.

Currently a revolution is taking place in biomedical science. 'This revolution centres upon (aptly named) free radicals'. The most famous of these is nitric oxide (NO).

Nitric oxide is a noxious chemical spewed out by car exhausts and power stations. For years it was considered to be one of the most poisonous gases known to man. However, in the 1980s scientists discovered that many cells of the body also produce nitric oxide. Hundreds of research papers have been produced in recent years investigating this short-lived compound. It is currently a more popular research topic than AIDS, Alzheimer's and arthritis. NO has revolutionised scientists understanding of blood pressure and the whole manner by which cells communicate.

It is thought that when released by the body in minute amounts it is capable of carrying biochemical signals from cell to cell resulting in a whole array of bodily events. In circulation NO helps to control the bore of the blood vessels and hence blood pressure. In the nervous system it is thought to be implicated in memory. In the immune system it purges both foreign bodies and tumour cells. The medical profession have realized NO's importance in many conditions not just high blood pressure but also stroke, septic shock, clotting disorders and even impotence.

The mode of action of NO is its most controversial aspect in terms of traditional understanding of cell biology. To start with NO is what chemists call a free radical. This means that it carries an unpaired electron and is therefore highly reactive, unlike any other molecules in the body's well- documented and well-balanced signaling system. NO liberated from cells is converted within a split second to nitrogen dioxide NO2 by combining with oxygen. Most of the both's other communication molecules are complex by comparison, molecules such as amino acids, catachol amines and small peptides. These conventional message transducers deliver signals by latching on to specific receptor molecules. A classic example is the catachol amine adrenaline latching onto beta receptors. This is usually described by a lock and key analogy. The mechanism of NO goes against this completely by penetrating cells directly. Once inside cells it stimulates the production of a small nucleotide called cyclic guanosine monophosphate or cGMP. This cGMP induces a host of functions ranging from muscle relaxation to slowing down blood clotting.

The importance of NO was first discovered in the regulation of blood pressure. NO was found to cause blood vessels to dilate by relaxing the muscles in the vessel walls. Blood vessels are made up of layers of muscular, elastic and fibrous tissue, and have a lining called the endothelium. The endothelium releases NO which drifts into the surrounding layer of muscle. There it triggers the events that make the muscle relax at the diameter of the vessel then widens. This process is controlled by the mechanical effect of the blood flow. When blood rushes over the cells of the endothelium it causes them to distort slightly. This distortion results in the release of NO. From this it can be seen which in turn sends messages to the vessel walls via a whole arm of receptors and transmitter muscles. The balance between the central nervous control and local control is not well understood. For years doctors have used drugs that affect the nervous control to lower blood pressure with apparent success, for example beta receptor blockers. However the result of the various NO experiments indicate that the nervous system is comparatively insignificant in the regulation of blood pressure. The mysteries of beta-receptors and there complexities are far from solved, yet these are supposed to provide the scientific bases of high blood pressure tablets, such as beta blockers. 'There must be a continued balance between these two powerful forces. - the local vasoconstrictor control and the central vasoconstrictor control.' says Sir John Vane, of the William Harvey Institute, London.

The theories of circulatory control have been revolutionized by one man. Salvador Moncado, who first documented the role of NO in blood pressure and clotting: 'We worked for hundreds of years thinking that the arterial system is a system of resistance vessels, when conductance is probably the better concept to use - which is the inverse of resistance. 'This has resulted in a conceptual reversal of all research in the field of high blood pressure. The novel theory has cast doubt on the mechanisms of all the blood pressure lowering drugs that have been used, and yet these drugs do appear to work. This has parallels with the use of the drug aspirin, which has been used for decades for various ailments, but theories of its mode of action were only documented in the late 1970s. What came first - human theories or the practical results? A current controversy is whether we should consider high blood pressure to be the result of too much adrenaline or too little NO.

Doctors have unknowingly utilized the NO system for years. Since 1867 amyl nitrite and nitro-glycerine have been used to relieve the horrendous heart pains experienced by sufferers of angina pectoris. Doctors knew that these nitrogen containing drugs dilated blood vessels and reduced blood pressure. But the exact biochemical Involvement in scientific research should always convince us that humankind has a very limited understanding of the universe and that most of the work done by us only involves giving names to existing phenomena.

Examples of this are not only confined to biology. A recent discovery has rocked the world of cosmology, with much more importance to Muslims. The data that have come back to earth from the Bubble telescope suggest that the universe is only 8 billion years old. Scientists consider these to be the most reliable data involving the most elaborate experiments performed by humans on this subject. Yet Big Bang theory calculations tell us that the universe is no younger that 16 billion years. The best real data tell us 8 billion years: the calculations from theory tell us 16 billion. The inadequacy of theories could not be more dramatically demonstrated.