The Spark of Life: Electricity in the Human Body (32 page)

In contrast to the nerve–muscle junction, where acetylcholine is the main transmitter, a cornucopia of different transmitters and their receptors are found in the brain. The main excitatory transmitter in the brain is glutamate – better known perhaps as the artificial flavouring in many Chinese dishes. Too much glutamate leads to over-stimulation of the target cell and can cause its death. Glutamate is therefore something of a Jekyll-and-Hyde molecule, essential for normal brain activity, but with the potential to destroy nerve cells completely. Consequently, cells have evolved ways to rapidly reduce the brain glutamate concentration to a low level, and transporters that capture extracellular glutamate and pump it back into cells are found at all glutamate release sites. The main inhibitory transmitter in the brain is gamma-amino-butyric acid (GABA), and that in the spinal cord is glycine. Many problems arise if any of this triumvirate of transmitters, or their receptors, are altered, or if we consume drugs or toxins that interfere with their function.

On the Horns of a Dilemma

In 1974, and again in 1997, Ethiopia was gripped by famine. The Western world watched in shock as horrific images of emaciated children and adults were beamed straight into their living rooms by satellite television. Food aid programmes burgeoned.

Unknown to these observers, a second tragedy was also unfolding. Many of the sufferers were reduced to crawling, not through weakness induced by starvation, but as a result of a poison contained in the only food available to them. A local doctor, Haileyesus Getahun, travelling in the remote and beautiful highlands of northern Ethiopia, described how he met a family of six, who ‘attempted to offer the traditional respect by bowing but unfortunately to no avail. All but one girl were crawlers’. The mother had to be tied with a rope to the wall of the hut to prevent her from falling down while grinding grain, and the family was totally dependent on relatives and neighbours for survival. They were tragic victims of a recent epidemic of lathryism – a crippling paralysis caused by eating the grass pea
Lathyrus sativa
.

The grass pea has been cultivated in South Asia and Ethiopia for over 2,500 years. It is a popular crop because it is cheap and easy to grow, withstands drought and flooding, is resistant to insect attack and produces a good yield of highly palatable seeds. It is also often the only food plant to survive extreme drought. Thus it sounds like the perfect crop for areas prone to famine conditions – except for one small catch. The plant contains high levels of a potent nerve toxin with the unpronounceable name of β-
N
-oxalylamino-
L
-alanine (usually abbreviated BOAA). BOAA specifically damages the motor nerves that control movement for, like glutamate, it is an ‘excitotoxin’ – a poison that acts by stimulating nerve cells so much that they die.

BOAA binds to glutamate receptors on motor nerve cells in the brain. These receptors are themselves ion channels, and glutamate binding opens the pore, allowing calcium ions to flood into the cell. Because too much calcium is toxic to nerve cells, the continuous excitation of glutamate receptors by BOAA eventually results in nerve cell death. As a consequence, those who eat the grass pea for long periods develop a flaccid paralysis of the legs and are reduced to crawling. There is little or no recovery, even after consumption ceases.

Lathryism is the oldest neurological disease known to man. As long ago as 400
BC
, the famous Indian physician Charak recognized that it was associated with excessive consumption of the grass pea, and about a century later Hippocrates wrote that at Ainos ‘all men and women who ate peas continuously became impotent in their legs’. The first account to clearly establish the link between lathryism and grass-pea consumption was that published in 1844 by Major-General William Sleeman in his book
Rambles and Recollections of an Indian Official
, which described an outbreak of lathryism affecting both cattle and humans in the Saugor district of Central India.

Despite this knowledge, however, tragedies continued to happen. During World War II, the inmates of a German concentration camp at Vapniarca on the Ukrainian border were given a daily ration of grass pea and bread. Within three months over 60 per cent of them had developed lathryism. The cause was eventually identified by one of the prisoners, who was himself a victim, and the problem was solved by removing the grass pea from the prisoners’ food. This incident led to recognition that consumption of the grass pea as a major part of the diet over a three-to-four-month period is required to cause paralysis.

Unfortunately, in some circumstances, people are faced with a stark choice between starvation and lathryism. In 1997, the grass pea was the only crop that survived the severe drought in Ethiopia, and it was consumed in many different forms. Although the plant was known to be harmful, the exact nature of the problem and how to prevent its effects were only poorly understood. Health workers were at a loss and advised the community to avoid contact with the steam or the drained-off water of the cooked grass pea – a common misconception that is inaccurate and of little value. No information pamphlets were available, and many communities were so remote they could only be reached by mule or on foot. The epidemic continued for a further two years, until grass-pea consumption fell.

Too Much of a Good Thing

Lathryism is not the only disease caused by hyper-stimulation of glutamate receptors. Early one morning in the summer of 1961, the coastal town of Capitola in California was attacked by an enormous flock of sooty shearwaters. Hundreds of them besieged the town, slamming into houses, dive-bombing people, falling lifeless from the sky and staggering around vomiting fish. People woke to find the streets littered with dead seabirds. The event so intrigued Alfred Hitchcock that it influenced his production of Daphne du Maurier’s short story, ‘The Birds’, and he even included a reference to the Capitola attack in his film. Investigation of similar incidents that occurred subsequently showed that they were due to domoic acid, a poison that is made by phytoplankton and accumulated at high concentrations by creatures further up the food chain. The shearwaters had picked up the poison from the anchovies on which they had been feeding.

Shellfish also accumulate domoic acid. This led to a mass outbreak of shellfish poisoning in Canada in 1987. More than 200 people who had eaten blue mussels were affected. In addition to vomiting and diarrhoea, many suffered disorientation, memory loss, seizures and coma and about a quarter of them also lost their short-term memory, in some cases permanently. Autopsies on the brains of four people who had died showed that their hippocampal neurones (which are important for memory) had been destroyed. Domoic acid kills neurones by binding very tightly to glutamate receptors of the kainate variety and causing them to open; the result is an influx of calcium ions that kills the nerve cells.

A number of fungi also produce compounds that activate glutamate receptors, which explains why their consumption causes dizziness, delirium and euphoria. The sodium salt of glutamate (monosodium glutamate or MSG) is a flavour enhancer that is added to numerous foods, often under the name of ‘hydrolyzed vegetable protein’, to improve palatability. It has received a bad press ever since it was suggested to provoke nausea, dizziness and a splitting headache – the famous ‘Chinese restaurant syndrome’. Most of the brain is protected from the effects of MSG by the blood–brain barrier, but a few nerve cells lie outside this protective barrier. In young mice, these cells are vulnerable to the toxic effects of high levels of MSG and if they eat too much they became extremely obese as the neurones that regulate body weight are selectively killed. Numerous safety studies, however, have shown that MSG has no adverse effect in humans at concentrations very substantially higher than those used as a food additive, and double-blind trials even failed to reproducibly demonstrate that MSG causes Chinese restaurant syndrome. Nevertheless, this did not stop MSG being the focus of the ‘Soup Wars’ campaign. The battle began when the Campbell Soup Company ran an advertisement featuring its own soup as being made of 100 per cent natural ingredients and unflatteringly contended that its competitor’s Progresso line of soups tasted of MSG. The General Mills Company, who make Progresso soups, counter-attacked, pointing out that in fact many of Campbell’s soups contained MSG, whereas many of their own soups did not. It also declared it was removing MSG from all its soups and challenged Campbell to do the same. And so it went on.

Scared Stiff

Sudden noises can make all of us jump. But imagine if every time you were startled your muscles seized up so severely that you froze rigid and toppled off your chair, or fell flat as a plank, like a clown in a circus act. This can happen to people with startle disease. Because they find their arms become stiffly clamped by their sides, they are unable to protect themselves when they fall and consequently may suffer multiple injuries. Babies with startle disease can be so severely affected that their spine arches backwards, as if in a tantrum, and their respiratory muscles seize up so that they suffocate and die. The disorder is sometimes known as stiff-baby syndrome.

The symptoms of this extraordinary disease are similar to those of strychnine poisoning, which provides a clue to its origin. The common cause is loss of glycine receptor function – either due to a mutation, as in startle disease, or to inhibition by strychnine. Glycine is one of the main transmitters at inhibitory synapses in the spinal cord and brain stem. It is released from inhibitory nerve cells and interacts with glycine receptors in the post-synaptic nerve cell membrane, opening an intrinsic ion channel that is permeable to chloride. This damps down the electrical activity of the target cell and prevents it from responding to excitatory inputs. Such inhibition is essential for normal function. The muscles that move our limbs tend to come in opposing pairs, one of which flexes the limb and the other which extends it. It is crucial that when one muscle is stimulated to contract the other relaxes, for if both contract simultaneously the limb becomes stiff and cannot move. People with startle disease cannot respond to the glycine released from their inhibitory nerves, so their opposing muscles fail to relax. As both muscles contract simultaneously, they become rigid when surprised.

Although this disease has some similarities with that of the Tennessee myotonic goats described earlier (in both cases the muscles stiffen up) it has a very different origin. Startle disease is a problem of the central nervous system, which fails to provide the muscles with the correct signals. The muscles themselves are normal. In contrast, the nerves of the myotonic goats are unaffected; it is the muscles that are defective.

‘The Mysterious Affair at Styles’

Late one night, Mrs Emily Cavendish, a wealthy widow, was found dying at her Essex country manor house, Styles Court, from what later proves to be strychnine poisoning. Agatha Christie’s famous detective Hercule Poirot unravels a series of intricate twists and turns in the novel to prove that her new husband and his lover are the culprits. Strychnine has been used in many famous cases of poisoning, both real and fictional. The Lambeth serial killer, Dr Thomas Neill Cream, invited prostitutes to take a drink with him, spiked their drinks with strychnine and left them to die in agony. As strychnine is one of the most bitter substances known, the drinks must have been sweetened to disguise its taste, or the girls must have been sufficiently inebriated not to have detected it. It was also once used as a rat poison.

Strychnine poisoning resembles startle disease because the drug blocks glycine receptors, rendering them non-functional. The toxin was first isolated from the beans of the plant
Strychnos ignatia
, which was named after Saint Ignatius of Loyola, the founder of the Jesuits. It is also found in the seeds of the Strychnine tree (
Strychnos nux-vomica
). Intriguingly, strychnine was once used as a stimulant, albeit at concentrations lower than that which cause severe toxicity. As might be expected, this sometimes led to accidental overdoses. A medical student, writing in 1896, described how he took it while studying for an examination because he was feeling run down. His calf muscles began to stiffen and jerk, his toes curled up, he saw flashing lights and he broke out in a cold sweat. He wrote that he ‘knew something serious was developing’ and so crawled to his medical case and drank potassium chlorate (an anaesthetic). He quickly lost consciousness and fell into a profound sleep ‘awaking in the morning with no unpleasant symptoms’ but a desire to be on the move and a temporary stiffness in the jaw. Not, one imagines, an experience he wished to repeat.

Brain Storms

Loss of inhibition in certain brain circuits can also trigger epilepsy, a sudden uncoordinated burst of excess electrical activity that resembles an electrical storm of the brain. Fyodor Dostoyevsky was probably the most famous epileptic in history. He recorded 102 seizures in his notebook and incorporated his experiences into his novels. Fits or seizures tend to be unique to the individual, for there are many types of epilepsy and many causes, but they can be broadly grouped into two main kinds. In petit mal or absence seizures, the patient goes blank for a few seconds, staring into space and seemingly switching off from the world around them. More dramatic are the convulsive seizures in which the victim’s limbs twitch and shake uncontrollably because the electrical storm influences the nerve cells that regulate their limb muscles. In some people the convulsions are highly localized and affect only a small group of muscles, whereas others may experience a grand mal seizure that is associated with generalized convulsions and often loss of consciousness.