From Poison Arrows to Prozac. Stanley Feldman
and for all, a debate that had engaged many eminent scientists during the mid-twentieth century. The dispute centred on the various claims and counterclaims as to the manner in which the brain passes on its instructions to the body. It demonstrated the important role that chemicals, produced in the brain and nervous tissues, play in this process.
It would have been impossible for human development to have occurred without the evolution in this chemical messenger system. Without the flexibility provided by additional messenger systems the brain would not be able to meet the requirements of an increasingly sophisticated and complex lifestyle. It is through learning how curare affects these systems that the subtle changes that have occurred in these mechanisms during evolution have come to light. It is these changes that have allowed us to develop the range of responses necessary for our present lifestyle.
This new understanding has led to the development of drugs to control an excessive activity of these responses or to supplement a failing system, to perfect existing drugs and to develop new, more specific agents, with fewer side effects. It is probable that in the future it will lead to a cure for conditions such as the memory loss that occurs as we get older, Parkinson’s disease, manic and depressive states, inappropriate emotional responses and many other disabling diseases.
This story that started with the South American arrow poison is not yet complete.
In telling this story in a way that is readily understandable I have tried to reduce technical jargon to a minimum, even though this has meant omitting details that might have been more satisfying to the tyro. I am aware that I have taken some leaps of faith. I have done so freely and in doing so I have promoted my own views about the way curare works. I have done so in a Popperian way,1 aware that future research may prove them to be wrong. For these transgressions, I plead mea culpa; my excuse is that they provide a better explanation of what happens than any alternative, more conventional theory.
If I have entertained the reader with a new insight into an amazing, fascinating story, I will be satisfied. If I have occasioned him or her to look in a new light at the way the physiological processes of the body are controlled, I will have truly fulfilled the purpose of this book.
1 Karl Popper (1902–94) was an Austrian-born British philosopher who argued that scientific theories can never be proved to be true, but are tested by attempts to falsify them.
Every one of the myriad cells that make up our bodies contains a minute drop of seawater. Not the seawater of today but as it was at the very beginning of life, in the vicinity of the underwater thermal vents that spew minerals into the ocean from below the Earth’s crust. It was here that the first forms of life are believed to have evolved, thousands of millions years ago. The contents of this fluid, inside the cells, are the same whether it is from the cells, of the heart, the pancreas, the brain or the spleen. It contains a similar concentration of salts, such as sodium, potassium and calcium, and the same minute amount of oxygen. The nature of this salty fluid, the ‘intracellular water’, has to be maintained within strict limits. If the contents change significantly, all the various processes necessary for life will fail.
Not only is the formula the same for the fluid inside all the cells of one’s body, but it is much the same as that in the cells of every mammal, irrespective of its diet or the climatic conditions in which it lives. We have much the same intracellular water as the elephant, the rat and the hippopotamus. This is no coincidence; it is the result of a common evolutionary history. It is a story that starts at the beginning of life on Earth.
Although no one can be certain as to the exact origin of life all the evidence points to it starting in the seas that covered much of Earth about 3,500 million years ago, on the ocean floor, where it existed as an immobile slime. It has been suggested that it originated with the formation of simple chains of chemicals, including a form of a primitive nucleic acid,2 the harbinger of DNA, that crystallised out from the salts dissolved in the sea. Chemicals dissolved in water will form crystals spontaneously if the concentration and temperature is right, just as substances, such as sugar and salt, crystallise out of water at a given temperature and concentration. In order for this process to become the precursor of life it would have to have been continuous and the crystals themselves self-replicating.
What is generally accepted is that, after many millions of years, something happened that suddenly caused an evolutionary explosion about 600 million years ago. This was towards the end of the greatest ice age that the planet has ever experienced, when glaciers extended almost to the equator, the time of the so-called ‘snowball earth’. It was at this time that many forms of multicellular life appeared.
What caused this extraordinary spurt in the development of life forms? Many explanations have been offered such as a change in temperature or in the composition of the atmosphere. The high CO2 levels that had prevailed at the time of the great freeze (some 100 times the present concentration) declined and a significant amount of oxygen appeared, for the first time, in the atmosphere. However, the most likely explanation is that it resulted from the development of the cell membrane.
By trapping a tiny drop of water within a membranous, semipermeable envelope, the cell wall, it would have been far easier for the cell to maintain a stable concentration of chemicals within its internal environment. In this way it would have been able to provide the conditions for the continuous production of the chains of chemical substances that are essential for life.
Had it not been for another remarkable event, evolution might have become stuck at this point. Single cells, or thin sheets of identical cells, could control the contents of their internal water as long as they remained immersed in the constant environment provided by the sea. Any cells that were not directly bathed by seawater would have been in danger of drying out. What made the next step in the evolution of more complex forms of life possible was the appearance of special organs to monitor changes, such as drying out, and to link these to some mechanism that would allow it to protect itself. This required a communication system to be developed.
The various steps in this evolutionary pattern are speculative, but one can make a reasonable guess as to how they came about. Some indication is afforded by studying embryonic development and the stages that animals, such as the frog, go though in their maturation process. It starts with a single fertilised cell, the ovum, and develops into an embryo containing many apparently identical cells into a stage at which cells with differing functions start to appear. This allows its maturation into a fishlike tadpole, which lives in water and eventually emerges from its watery environment as a young, air-breathing frog.
It is probable that the only form of life that was capable of leaving the primordial swamp and surviving on land was composed of one or more simple, identical cells. This form of life would have survived by absorbing water and dissolved nutriment through the thin membrane covering the cell. The main danger to its survival would have come from changes in temperature or from a drying out of the environment. This dehydrating effect would have produced changes in the local concentrations of chemicals, such as sodium, potassium, chlorine and calcium, within the cell. It is believed that it was these alterations in the local concentration of salts that initiated the process of ‘differentiation’, in which new types of cells were formed. It was this process that led to the development of more complex organisms.
With the passage of many millions of years the atmosphere became drier and temperature fluctuations more dramatic. Only those organisms that produced some means of adapting to these changes survived. Those that survived developed groups of cells that had special functions. These were the forerunners of the sensory and motor organs found in more advanced forms of life. Because of the drier environment in which they now existed, the surface of these early animals became covered with a thick skin or carapace to limit fluid loss. This impermeable covering would have prevented the organism from taking in fluid and nutriment through its surface and necessitated the development