So much of modern medicine relies on our understanding of the physiology of the human body. It is easy to take this vast archive of knowledge for granted, and it is sobering to reflect on the relatively recent past, when the mechanics of the body were a mystery, subject to guesswork and superstition.
Figure 1.
Stanley Feldman
Metro, £14.99, pp 244 ISBN 1 84358 137 X www.blake.co.uk
Rating: ★★★
In the mid-19th century the great French physician Claude Bernard predicted that toxins could be used as instruments and that, by elucidating their mode of action, insights could be cast on the structure and functioning of the body.
This concept forms the backbone of Feldman's fascinating book. The toxin in question is curare, originally known as woorari by South American aboriginals, who used it on their poison arrows. Feldman walks us through history, showing the way studies on this toxin helped to lead to the present day understanding of nerve physiology and, in particular, the way in which acetylcholine released from nerve terminals binds to the receptor on the motor end plate of muscle. This in turn paved the way for the development of neuromuscular blockers, an essential group of drugs in modern anaesthesia, the introduction of which has contributed to a 40% decrease in anaesthetic mortality.
It is always revelatory to consider the breakthroughs that have occurred in relation to any single line of study and its related branches. The chain of research that led to our present understanding of nerve physiology started around 265 years ago, when the first samples of crude arrow poison were brought to Europe by voyagers sailing back from South America, with records of experiments in Leiden in Holland recorded in the 1740s. Bernard's seminal experiments, starting in 1844, were an important step in showing that curare prevents the message carried in nerves from being translated into muscular activity. Then followed almost a hundred years of progress, taking in the experimental use of curare in tetanus and rabies, the proposal of its use for muscle spasms by Richard Gill in the 1930s, discovery of its structure by Harold King in 1935, its subsequent use in anaesthesia, and its role in illuminating the five unit structure of the acetylcholine receptor on motor end plates of muscles.
A book focusing on one very specific area can easily become dry or esoteric, but Feldman captures our interest, both with his clear explanations of the research and the background information, which spices up the facts with colourful snippets of historical interest and peripheral information. Thus we obtain flashes of insight into areas as diverse as the public health problems of Victorian England, the differences between anaesthetics given in the United States and Europe in the mid-20th century, and recent applications of drugs developed as a result of knowledge imparted by curare, such as organophosphate insecticides, which act by inhibiting the enzyme that breaks down acetylcholine (cholinesterase), thereby inducing seizures and death. The concept also lies behind the more chilling development of nerve poison organophosphates such as sarin.
The appeal of this book is not limited to anaesthetists and physiologists: it is also of great value as a chronicle of the meticulous research that underpins evidence based medicine.