From Poison Arrows to Prozac. Stanley Feldman
areas through which food and water could be ingested.
As the environment dried out further and changes in the temperature become more extreme, the chances of survival depended on developing some means of locomotion to allow it to escape from a dry, hot area for a nearby site where water, nutriment and shade were available. This required some means of detecting changes in the environment, a sensory system, and a means of conveying the information from these sensory organs to the organs responsible for propulsion. For this to be possible a messenger system had to be developed.
Chemicals, acting as messengers, served this function. The first such chemical messenger must have been formed from substances that were abundant in Earth’s atmosphere at that time, such as ammonia, carbon dioxide and water. It is probable that this was either acetylcholine or a similar substance. It would have been released in response to an alarm signal from cells capable of sensing changes in the outside world.
It is quite possible that the present-day role of acetylcholine, the most ubiquitous of all the chemical transmitters in the animal kingdom, dates back to these primitive times. It would have functioned in much the same way as it does today in the clams and oysters on our seashores. In these bivalve molluscs, acetylcholine is released into the fluid bathing the tissues in response to a signal produced by touching the shell. It causes the strong muscle that closes the two halves of the shell to contract.
Even today an atavistic enzyme that destroys acetylcholine is present in the bloodstream of man. No physiological function can be ascribed to this enzyme; indeed, a number of people live perfectly normal lives without it. It is possible that its presence is a footprint of the evolutionary stage when acetylcholine was released directly into the tissue fluids.
As evolution progressed and these organisms became more complex, special structures capable of detecting changes in the outside world – such as eyes and ears – developed in parts of the body that were remote from the muscles involved in making an appropriate response. This necessitated a more sophisticated means of communicating information from one part of the body to another. This need was met by the development of cord like nerve trunks as simple extensions of nerve cells. They connect the sensory organs to the brain and carry instructions from the brain to other parts of the body.
By this means it was possible for the transmitter, acetylcholine, to be released at nerve endings some distance from the sensory organ itself but close to the sites responsible for initiating a response. Acetylcholine then became a specific transmitter, passing on the messages carried in the nerves to the muscles, heart and circulation.
The next stage in this story occurred when animal life evolved still further and started foraging for food and shelter. Newer transmitter substances appeared that helped prepare animals for this new challenge. Later still in the evolutionary development of the brain, we find more sophisticated transmitters appearing associated with the response to hunger, mood, sexual arousal and memory. However, acetylcholine continues to provide the background activity that controls the release of all of these substances.
Curare
Without chemical messengers, the evolution of complex forms of life would have been impossible. The first intimation that such a system might exist came from the French physiologist Claude Bernard in the nineteenth century. He suggested that the ultimate purpose of all the control systems of the body – which are constantly in action, although we are not aware of them – was to maintain the integrity of the bodily fluids within the narrow limits necessary for life. This he proposed was the essential condition for la vie libre – life in a constantly changing external environment.
This was the position until about sixty years ago. By 1930, evidence was emerging that the chemical acetylcholine was involved in adjusting the heart rate and that it was also released when muscles responded to nervous commands. Over the next two decades there was an acrimonious debate as to the role it played in these responses imitiating them, while others ridiculed the idea.
It was at this point in the argument that the investigation into the role of acetylcholine in muscle activity converged with studies into the way in which the South American arrow poison, curare, killed its victims. There was a continuous thread in the experiments involving curare which stretched back over four centuries. It started with the early explorers to the New World, who described the terrible manner of the death of those poisoned by darts anointed with this poison and continued intermittently until the 1930s, when its action was finally demonstrated.
This was one of those coincidences that occur from time to time in scientific investigation when a discovery in one discipline provides the means of making a quantum leap in another. In this case it was the understanding of the way curare paralysed its victims that allowed the researchers at University College in London to demonstrate, unequivocally, that the brain controlled the functions of the body by means of chemical messengers such as acetylcholine. It was a discovery that changed the face of medicine.
This story begins with the discovery of America by Christopher Columbus in 1492 and the subsequent voyages of explorers to the jungles of South America.
2 It has been suggested that primitive peptide nucleic acid reached earth on meteorites and from the large amounts of interstellar dust that rained down upon its surface after it was formed. Meteorites and interstellar dust contain a high concentration of organic chemicals, including amino acids and purines, the precursors of DNA.
The South American Arrow Poison
A spice is a dried seed, root, bark or fruit used as a food additive for flavouring and indirectly for preventing putrefaction and the growth of pathogenic bacteria.
Spices, such as cloves, have been used to flavour foods since ancient times. The Bible tells, in Genesis, how Joseph was sold into ‘the slavery of spice merchants’ by his brothers. There are frequent references to the use of clove oil in Roman literature, where it was used to mask body odours and for religious rituals. However, until the Middle Ages, the practice of using spices in the preparation of food was largely restricted to the Middle East. In these countries, cinnamon, black pepper, cloves, saffron, cassia and ginger were used by those wealthy enough to afford them.
It is probable that the taste for these spices was brought to Europe by the Crusaders. At first they were used mainly by the rich merchants of France and Spain, but eventually their use spread to England. By the fifteenth century the demand for these spices had spread throughout the whole of northern Europe, although they were always too expensive to be used in everyday cooking. In spite of their cost, the demand for pepper, cinnamon, cloves, nutmeg and ginger was huge.
By the end of the fifteenth century it was estimated that about 1,000 tons of pepper and 1,000 tons of other spices were imported into the Port of London each year. Pepper was widely used to disguise the flavour of meat from animals that had been slaughtered before the onset of winter and kept from going bad by salting and pickling. Without the addition of a spice the meat was invariably so salty that it had to be soaked in water to make it eatable.
So it was that, in the fifteenth and sixteenth centuries, shops selling pepper and other spices and merces were commonplace in the streets and alleys of towns such as London. The trade in pepper was so important that it led to the establishment, by Royal Charter, of the Company of Pepperers. It eventually became a part of the newly formed Grocers Company.
Unfortunately, by the second half of the fifteenth century, pepper was in short supply and the price had escalated, putting it out of reach of all but the very wealthy. Part of the increase in cost was due to a growth in demand, as it became more and more fashionable, but most of the price rise was due to the insecurity and expense of its transportation to England from the Orient and the Far East, where it was produced.
Almost all the spices came from the Moluccan (or Maluku) Islands of the East