The Poison Penalties: Uses, Abuses and Consequences
Chapter 17
MANY POISONS HAVE BEEN used in the past as medicines, and some are still used today because the benefits of treatment outweigh the risks of their use. Some of these poisons were used a great deal in the past, even though we now know that they were totally ineffective and did nothing at all.
For example, in the nineteenth century, phosphorus was widely used in medicine. Doctors had discovered that the brain contained a lot of phosphorus and so thought that more would be a good idea. It was given in small doses for a wide variety of conditions, from epilepsy to cataracts, and even pneumonia and cholera. Tonics and toothache treatments containing it were sold, and phosphorus was still being prescribed for bone conditions in the 1920s. By the 1940s, however, it was rarely used, and eventually doctors realised that phosphorus was absolutely useless as a medicine, having no therapeutic value at all.
Would you reuse your laxative?
In the Middle Ages, pills made from the metal antimony were sold, believe it or not, as reusable laxatives. This metal has a toxic effect on the bowel, tending to cause diarrhoea. So, if you were constipated, you swallowed the antimony pill, which was about the size of a pea, and then waited for the desired effect, which duly returned this perpetual pill for reuse at a later date, providing you remembered to look for it.
Antimony was also used to make special goblets, called emetic cups, into which a little wine was poured and left overnight after an evening of feasting and drinking. This wine, laced with antimony, was drunk the following morning, as a cure for the hangover and the overindulgence from the feast of the night before. The irritant effect of the antimony on the gut induced vomiting, and so emptied the stomach.
Paracelsus vs. Galen
Antimony became very popular in the late Middle Ages when the famous physician Paracelsus advocated its use. Paracelsus was the Latin title adopted by a gentleman with an impressive name: Philipus Aureolus Theophrastus Bombastus von Hohenheim (1493-1541). He could certainly sign his prescriptions faster using the name Paracelsus. He adopted this name because he considered himself to be ‘above Celsus’, who was a great Roman medical philosopher and forerunner of Galen. Until this time the works of Galen were the accepted version of medical authority and treatment.
Paracelsus challenged the Galenic authority and, while teaching at Basle University, he publically burnt Galen’s works and offered instead his alternative theory based on the use of metals and minerals rather than just herbal remedies. The description ‘bombastic’ came into use from his name, because he was so full of himself. However, it was Paracelsus who realised the importance of the dose of medication required, in relation to both the beneficial therapeutic effects and adverse toxic effects. He knew that a small dose of 5mg of antimony potassium tartrate would stimulate the metabolism and induce sweating, while a larger dose of 50mg would cause copious vomiting and damage the liver. Tartar emetic (antimony potassium tartrate) was consequently commonly used in the sixteenth century and thereafter to treat all kinds of ailments.
And so it was that mercury, lead, antimony, arsenic and their salts came to be used extensively as medicines for the next several centuries.
Dr William Palmer was a genial young man, a physician by profession, but a gambler too. He became known as the Rugeley Poisoner. He loved the good life, but he lacked the money to support his lifestyle, even though he owned several racehorses. His life appeared to be littered with a number of most unfortunate, though lucrative, fatalities.
First his mother-in law died, leaving him some property, and then a racing friend to whom he owed £800 died, thus wiping out the debt. Then the unfortunate doctor’s wife died, not so very long after he had insured her life for £13,000. He had only just made the first payment on the policy. It was not until some years later that these deaths came to be regarded as suspicious. His undoing was the death of his friend and fellow racehorse owner, John Parsons Cook. Mr Cook was taken ill and died in agony after a visit from Palmer.
They had attended Shrewsbury races together in November 1855, where Palmer, who was already in deep financial trouble, lost heavily while his friend Cook was on a lucky streak. They went to celebrate his winnings in the bar but John suddenly collapsed. The doctor showed some concern for his friend and then volunteered to pick up his winnings for him. He used this money himself, to pay off his most pressing debts, and then arranged for his friend to be taken to the Talbot Arms Hotel, which just happened to be directly across the road from Palmer’s home in Rugeley, Staffordshire.
He continued to treat his friend for several days until he died on 21st November 1855. Cook’s stepfather, however, became suspicious and a post-mortem was performed by a leading toxicologist, Professor Dr Andrew Taylor. This doctor made his name by writing the first textbook on medical jurisprudence. He found traces of antimony in the dead man’s stomach. Palmer was duly found guilty of murdering his friend Cook, and was hanged outside Stafford Jail on the 14th June 1856, at the age of only 32. It is thought that he may have murdered as many as 14 people in his short medical career.
Patent medicines
In medieval times, the spicers (the retail sellers of spices) also began compounding and selling medicines. By the start of the fourteenth century, they had joined forces with the pepperers (the wholesale sellers of spices) to form the apothecaries. The first records of an apothecary shop date from 1345, and in the eighteenth century the chemists and druggists appeared. They sold medicines, such as their own ‘nostrums’, as well as patent medicines, in addition to dispensing prescriptions.
In the seventeenth century, Nehemiah Grew, a botanist and physician, patented magnesium sulphate. This was the very first patent medicine. He had it extracted from the spa at Epsom, which was in fashion at the time. He called his medicine Epsom Salts and sold it as a cure-all, for this was the heyday of ‘quack medicines’. It has been used ever since in skin preparations, or added to bathwater, but even today is still used by some older people as a treatment for constipation. Magnesium hydroxide, also known as Milk of Magnesia, is also used for indigestion and constipation, but overuse of this apparently innocuous digestive aid can lead to toxicity, resulting in lethargy, muscle weakness, confusion and even, eventually, to death.
Patent medicines, with royal letters patent, granted to an individual, by the sovereign, the sole rights to make a unique product. These were deemed respectable, unlike the many useless ‘quack medicines’ sold widely since the 1600s. James’s Powders, comprising one part antimony oxide to two parts calcium phosphate, were patented by Dr Robert James in 1747. The patent cost him £150, a great deal of money in those days. The investment in this patent was obviously worthwhile as James’s Fever Powders were still on sale in chemists’ shops in the 1920s. Today the Patent Office confers such rights, but patents now generally only last for a term of 20 years.
Antimony for infections and parasites
Antimony preparations, together with those of arsenic and mercury, were used for hundreds of years as a treatment for syphilis. About 80 years ago, it was also found that antimony salts were effective medicines for a number of parasitic infections common in the tropics, such as schistosomiasis, leishmaniasis and trypanomiasis.
The chosen medication was given by injection, in carefully calculated doses, so that it killed the parasite, but not the patient. Fortunately, since then, most antimony-containing compounds have been superseded by far less toxic and far more easily administered drugs, such as praziquantel, in the treatment of some of these parasitic infections in the tropics which, even today, are still so common.
In November 2008, the television presenter and adventurer, Ben Fogle, contracted leishmaniasis while filming in Peru. The parasitic protozoan left him with an inch-deep hole in his arm, for which a course of daily injections of an antimony-containing drug was given for several weeks. The side effects of this type of drug are serious and make people feel very ill indeed; however, it is the only way to kill off this flesh-eating parasite.
Arsenic solutions
The effects of arsenic have been known since prehistoric times, and it has been used in medicine ever since for all kinds of ailments, including such widely diverse complaints as rheumatism, diabetes, malaria and consumption (the old-fashioned name for tuberculosis). Arsenic sulphide was used by Hippocrates, Dioscorides, Galen and Paracelsus and, during the heyday of quack medicine in the eighteenth century, arsenic became very popular indeed.
In 1780, a Dr Fowler concocted his ‘Solution’, which was quite simply a mixture of arsenic trioxide and potassium hydroxide dissolved in water, to which lavender water was added. The lavender water was included for its smell, which was intended to act as a warning to prevent accidental overdose. The dose, of only a few drops, was added to water or wine and taken as a general tonic, a popular cure-all, and was even used as an aphrodisiac. Doctors prescribed it to aid convalescence. Even Charles Dickens is claimed to have used it. Fowler’s Solution was still in use in the mid-twentieth century, although by then it was used only for skin complaints, and today it is no longer used.
In small doses, arsenic seems to boost the metabolism and increase the formation of red blood cells; however, prolonged exposure can cause dermatitis, and breathing arsenical fumes can cause lung cancer. The stimulating effect of arsenic was used in the past by unscrupulous trainers who doped their horses in the hopes of winning a race. Such doping is easily spotted, as a simple urine test will detect the presence of arsenic.
A derivative of arsenic acid, roxarsone, was used to fatten pigs and poultry, again utilising the stimulating effect that arsenic has on the metabolism. This food additive was removed from the animals’ food about a week before they were due to be slaughtered, to allow sufficient time for the arsenic to be excreted before the meat reached the butcher’s block. This tonic effect can be tried out by you, dear reader, simply by drinking Vichy mineral water, which contains about two parts per million of arsenic, derived from the particular rock strata Vichy water passes through.
In 1909, Paul Ehrlich found, after many years’ work, that an arsenical compound – the 606th he had tried! – could cure syphilis. He named this substance, Salvarsan, and it quickly became the standard treatment for syphilis until penicillin arrived in the 1950s. Salvarsan, also known as arsphenamine, was still being used to treat dysentery and sleeping sickness until eventually, in the 1970s, much better, more effective and less toxic agents were found for these diseases.
Arsenic is still in use today, but it is now only used in properly tested and approved medicines for treating a particular form of acute leukaemia. In this situation, when it is given in combination with other drugs, the ability of arsenic to stimulate the production of normal red blood cells is put to good use.
Deadly cyanide revisited
Although sodium nitroprusside contains cyanide, it is used to treat hypertensive crises and to reduce blood pressure during anaesthesia, in certain special types of surgery. It is also used to treat ergotamine poisoning and has even been tried as a treatment for Raynaud’s disease.
However, it is little used today, except in the case of an emergency, due to the risk of cyanide poisoning with its use. This same substance was used for many years by diabetics to test their urine for the presence of ketones that result from the partial oxidation of fats, which can occur if lack of insulin prevents glucose being used as a fuel by the body. Nowadays, most diabetics monitor their blood sugar level instead, as this gives a far more accurate real-time result and allows them to adjust their diet or insulin dose accordingly.
In 1982, a 12-year-old girl, four women and two men in the Chicago area of the USA all collapsed suddenly and died after taking Tylenol capsules. Tylenol is an American brand name for the painkiller paracetamol, or acetaminophen, as Americans call it. These poisonings were due to product tampering. The perpetrator was never caught, despite a large reward of $100,000 being offered by Johnson & Johnson, the manufacturers of Tylenol.
Investigation revealed that someone had apparently shoplifted packs of Tylenol from a number of small stores, emptied some of the capsules and then refilled the bottles with potassium cyanide, before replacing them on the shelves of different stores. The Tylenol bottles examined were found to contain different quantities of poisoned capsules – some as few as five, some up to as many as 30 capsules per bottle.
A wave of copycat tampering followed, with Lipton Cup-A-Soup in 1986; Tylenol again in 1986; Excedrin, a combination painkiller, also in 1986; Sudafed, a decongestant in 1991 and Goody’s Headache Powders in 1992; and there were yet more deaths. Before the Tylenol murders, tamper-evident packaging was little used, but since then the technology of this aspect of packaging has evolved and is now commonplace, for medicines and for many other products.
Marvellous or malicious mercury
Mercury compounds have been used in medicine for thousands of years, although today we now recognise the poisonous properties of mercury and its compounds. Calomel (mercurous chloride) was widely used from the late fourteenth century for several centuries as both a treatment and cure for syphilis. This treatment was effective in killing the causative micro-organism but the cure was risky, causing intense salivation and other toxic symptoms to the patient.
Calomel has long been used as both a laxative and a diuretic, as well as in teething powders, which were still on sale in the first half of the twentieth century; this latter use is described in detail in Chapter 13, The Noxious Nursery. The even more poisonous mercuric chloride, known as corrosive sublimate, was also widely used in the past, as a disinfectant. Mercury is still used today in traditional Chinese medicine, in cinnabar sedative pills and antidotal pills.
Metallic mercury was once widely used for skin complaints, made into ointments by being mixed with fats. Such salves first appeared in the thirteenth century. These applications also resulted in excessive salivation, a symptom of poisoning, because the mercury was absorbed through the skin and into the bloodstream, and so was distributed throughout the body.
Years ago, a nine-month-old baby girl with a bad case of nappy rash was prescribed ammoniated mercury ointment by her doctor. Although it worked well in clearing up the nappy rash, it gave her mercury poisoning too, which then also needed treating. Ointments containing mercury were phased out several decades ago, in favour of the far more effective antibiotics and antifungals we use today
Yellow mercury oxide ointment was sold as ‘Golden Eye Ointment’ for many years, until the early 1980s when it was discontinued in the United Kingdom because of its mercury content. However, some years later the brand name ‘Golden Eye’ was re-introduced, although the ointment and drops now sold under this name in Britain no longer contain mercury.
Most dentists still use mercury in amalgam fillings, this use being invented by an American dentist in 1895. Today, the alloy powder that is mixed with the mercury contains silver, tin, copper and even a trace of zinc. These fillings are considered safe for the patient; the main hazard is actually to the dentist and his workers who are in daily contact with the amalgam and the mercury vapour produced.
In the nineteenth century, mercurochrome was widely used as a general household antibacterial and antiseptic agent. Mercurochrome was a weak disinfectant, bright yellow in colour, which contained both mercury and bromine – its full chemical name was mercurodibromofluorescein. It was used medicinally, in solutions for bladder irrigation, as well as for bathing wounds, but deaths occurred due to skin absorption and shock. There were also cases of contact dermatitis and epidermal cell toxicity, as a result of which the use of mercurochrome was discontinued.
Thiomersal, or thimerosal in the USA, is a mercury-containing compound that was used as a preservative in biological products, including vaccines. This was a matter of controversy in recent years, for some parents believed that this source of mercury may have been the cause of autism in young children. Autism tends to manifests itself at about the same age as when the child receives the vaccination. The work of Dr Andrew Wakefield, which sparked this controversy in 1998, has now been discredited, but it is undeniable that there was a marked increase in the number of cases of autism diagnosed in the last decade or so.
Many causes for this increase have been suggested, but no single cause has yet been proved. Earlier and more accurate diagnosis is probably the best explanation. Dr Wakefield’s legacy came home to roost in 2008, when measles broke out in a number of places across the UK and some fatalities occurred. This only happened because so many parents decided not to let their babies have the MMR series of inoculations, a decade ago, which would have protected them.
Although research into this area continues, mercury as a vaccine preservative is now being phased out. The medicinal uses of mercury and its compounds are such that, today, the therapeutic benefit is far outweighed by the hazards. Consequently, clinical use has now been largely abandoned, except for those few mercury compounds still used in homoeopathic medicine.
Lead galore
Despite its toxicity, doctors have been using lead compounds as medicines for thousands of years. Medicines containing lead were used in the past for everything from gonorrhoea to neuralgia, from coughs to hysteria, although now we know better.
In the Roman Empire a physician to the emperor Tiberius is said to have invented diachylon plasters, which contain lead oxide and olive oil, for skin complaints. Unfortunately even then, women made use of the poisonous lead for their own reasons – they ate the plasters, as a means of procuring an abortion to terminate a pregnancy, as was mentioned in the previous chapter.
In the eighteenth century, in the heyday of quackery, lead acetate was used for skin complaints, for piles and even for cancer. Victorian doctors used it together with opium for diarrhoea: the lead paralysed the gut while the opium killed the associated pain.
The medicinal use of lead as an astringent skin lotion in the past has long since stopped; the lead acetate solution has been superseded by far more effective, though less toxic, preparations. However, lead acetate is still in use today in cosmetic lotions used to ‘restore’ colour to greying hair. Preparations such as ‘Restoria’ and ‘Grecian 2000’, which also contain sulphur, are sold for this purpose, the lotion meant to be applied to the greying hair to darken it. The solution works because the lead and the sulphur combine to produce black lead sulphide on the hair. Hair is dead tissue, so this treatment is not harmful; only a minute amount of lead would be absorbed through the scalp, and then only if any of the lotion came into contact with it.
Better with bismuth
Bismuth is a heavy metal that is only present in the human body in a few parts per billion. It is not involved in our metabolism in any way, but its compounds have found a specific use in medicine. In the 1780s, doctors began to prescribe bismuth mixtures for gastric complaints and peptic ulcers. Compounds of bismuth are still in use today in products such as Moorlands Indigestion Tablets and Pepto-Bismol, both for gastric complaints, as well as in some preparations for haemorrhoids.
Some bismuth-containing compounds are also active against Heliobacter pylori, the organism that can colonise the gut and cause gastric or duodenal ulceration. Although bismuth’s mode of action is still not fully understood, it appears to act on the mucus that protects the lining of the stomach, as well as de-activating the protein-digesting enzyme pepsin. While bismuth preparations are considered to be very safe, excessive use can cause liver damage and a characteristic blue line on the gums, which can persist for years. Injections of bismuth-containing compounds were used in the past to treat syphilis, and one containing both bismuth and arsenic was used as an oral treatment for amoebic infections; however, newer, safer and more effective drugs are now available. Bismuth compounds are also still used in homoeopathic preparations.
Happy halogens
Fluorine is a very potent antibacterial. It is the most reactive of the group of elements called the halogens; it is far more effective as a treatment than chlorine, bromine or iodine. Various drugs contain fluorine atoms in their molecules. With some, the action is so potent that a single dose is all that is required for treatment. Diflucan One, fluconazole, an anti-fungal agent, will treat vaginal thrush with a single oral dose of one 150mg capsule.
This same drug is also used for treating the life-threatening fungal infections suffered by transplant patients. This is not a new idea: flucloxacillin, an antibiotic of the penicillin family, also contains fluorine, and has been available for over 30 years. The antibiotics known as fluoroquinolones, such as ciprofloxacin, are used for infections that are difficult to treat with other conventional antibiotics. They also contain fluorine.
Bromine is another useful halogen. In the nineteenth century, mixtures of bromide salts were prescribed by doctors for the treatment of nervous complaints and epilepsy. They were the Victorian equivalent of tranquillisers, used to depress both mental activity and the sex drive. The reference during wartime to ‘bromide in the tea’ of the troops was a suggestion that they were dosed to ease tension and take their minds off their womenfolk back home. It is interesting to note that some spa waters owed their popularity in the eighteenth and nineteenth centuries to their high bromine content.
Bromides were widely used until the mid-twentieth century as sedatives for the mentally ill, but precise doses were needed for optimum effect. These are no longer used since benzodiazepines, such as Valium, better known now as diazepam, became available over 40 years ago.
Iodine was used for over 150 years as an antiseptic and disinfectant and is still much used today, particularly by operating theatre staff, as povidone-iodine for its germ-killing properties during surgery. Colourless iodine, marketed because it would not stain skin or clothing, does not have the same disinfecting properties as povidone-iodine, which is amber in colour, like the ordinary iodine solution. A great deal of iodine, as the radioactive isotope Iodine-131, was released into the atmosphere in the Chernobyl disaster, mentioned in the treatment chapter and Chapter 14. Taking potassium iodide tablets as soon as possible is the recognised treatment to protect the thyroid gland from damage by the radioactivity. Regrettably, such tablets were not readily to hand when Chernobyl blew up.
Quack cures with radium
Radium was regarded as a wonder drug a century ago, and quack cures using it were marketed within a few years of its discovery. Some of them remained on the market for almost 30 years. Radium Salve was a very weakly radioactive ointment marketed in Britain about 100 years ago.
In America, the ‘Cosmos Bag’ was a supposed radiation cure that was to be applied to arthritic joints. ‘Revigorator’ was a flask lined with radium, in which you left water overnight to drink the following morning. Another product was ‘Raithor’, a weak solution of radium salts, claimed to prevent disease. A steel magnate from Pittsburgh, Eben Beyers, drank a bottle of Raithor every day for four years, by which time he had severe radiation sickness and cancer of the jaw. He died in 1931, and the subsequent publicity about his death marked the end of such quackery.
Lithium for gout?
In the nineteenth century, taking the waters was still fashionable. In 1843, Dr Ure advanced a theory that lithium could be used to treat gout. He believed that taking certain lithium-rich spa waters would aid recovery. Because gout is exceedingly painful – being caused by the formation of uric acid crystals between the joints, particularly of the bones of the feet – Dr Ure probably made a tidy fortune from his spa water.
It was not until 1912 that Dr Pfeiffer showed that lithium actually slowed down the elimination of uric acid from the body, so making the condition worse rather than alleviating the problem. It was also shown that the concentration of lithium in the spa waters was far too low to have any therapeutic effect anyway – another quack cure discounted.
Lithium, however, does have its uses in modern medicine. It has been used for the last 50 years in the treatment of manic depression. Its use for this was discovered by accident by Dr John Cade, an Australian doctor, in 1949. He was trying to discover if manic depressive patients were producing an excess of some body chemical which might be causing their symptoms. He noticed that the experimental animals he was using had become very calm when injected with a lithium-containing solution. He then tried it on a patient who was so ill that he had spent five years in a secure unit.
This patient improved so much within a few days of starting this treatment that he was transferred to a normal ward and was eventually able to return home and even take up his old job again. Other doctors tried the treatment with equally impressive results, and this is now the standard treatment for manic depression (now called bipolar disorder).
Great care must be taken to get the correct dose of lithium for each patient. Regular blood tests are needed to monitor patients’ lithium levels, as the therapeutic level is not far below the toxic level. Patients taking lithium need to be aware that many other types of drug can interact with lithium. If the lithium level in the blood is allowed to rise too high, it can lead to toxicity, the symptoms of which are confusion and slurred speech. If left untreated, such toxicity can be fatal.
In the first half of 2009, a clinical trial started in which 220 sufferers of motor neurone disease (MND) will be given a daily lithium carbonate tablet for 18 months. There is evidence that this treatment might help sufferers of MND. At present there is no effective treatment for this progressive illness, but such a trial may show evidence of a slowing of the course of MND. This slowing may occur by promoting new nerve growth or by protecting existing nerves.
Normally, MND patients are only expected to live for about 15 months after diagnosis. Current treatment with riluzole can extend life by only about two months. Professor Stephen Hawking, now aged 66, discovered he had the disease over 40 years ago, and his survival is an exception to the normal rapidly progressive nature of this disease.
Danger! Treatment risks
Nitrogen mustards were originally developed as chemical warfare agents, but a number of them are now used as anti-neoplastic agents in the treatment of cancer. Great care must be taken by all the healthcare workers involved, such as doctors and nurses, when treating patients with these agents. Even the urine from patients receiving such treatment must be handled with protective clothing, including gloves, for 48 hours after treatment; such is the toxicity of these drugs.
Silver nitrate, which has antibacterial and antiviral properties, has been used since medieval times, when it was known by the impressive name of ‘lunar caustic’. It has long been used as a remedy applied to warts to remove them, and works by killing the virus causing the wart. Caustic pencils are still on sale today for this purpose.
The antimicrobial property of silver is also used in the treatment of burns, with compresses soaked in silver nitrate solution and cream containing silver sulphadiazine. Unfortunately, with large areas of raw tissue exposed following extensive burning, some cases of argyria – due to silver poisoning – have occurred because of the direct absorption of the silver by the raw tissue, which would not occur through normal skin.
Dressings and catheters containing silver are used today, both in hospitals by nurses treating patients and in the community, where the antimicrobial activity can be utilised against antibiotic-resistant strains of infective organisms. It is now possible to buy first aid plasters containing silver as an antibacterial from any local pharmacy.
Thallium was used in medicines in the past – as a hair remover for people about to undergo treatment for ringworm of the scalp. Hair loss is a symptom of thallium poisoning, so this ‘side effect’ was utilised, with thallium coming into general use as a depilatory for over 50 years. A number of cosmetic preparations containing seven per cent thallium acetate in a depilatory cream were available to purchase in the 1930s. However, following many fatalities from both systemic and topical treatment it was no longer used for such purposes. A number of cases have been described in earlier chapters.
Big bad Bs: brimstone, barium and boron
Sulphur was used in medicine since prehistoric times and has been prescribed by doctors for over 3,000 years. The old name for sulphur was brimstone, and a popular remedy for both digestive upsets and regularity in the past was ‘brimstone and treacle’. Its mode of action was as a laxative, the sulphur being converted to irritant sulphides in the gut. The modern equivalent, sulphur lozenges and tablets, were still on sale in the 1980s but have since disappeared from pharmacies. Sulphur was also used in creams, pastes and ointments to treat acne and scabies, a parasitic infection, as well as in lotions made with various organic solvents such as ether, alcohol and chloroform. These lotions were abused by ‘sniffers’.
Barium and many of its salts are very poisonous if absorbed by the body. In the early days of X-ray investigations of the gut, deaths occurred due to the unfortunate administration of some unsuitable barium salts. Barium sulphate was used for many years as a contrast medium in X-ray investigations of the stomach and intestines. This is perfectly safe because this particular barium salt is insoluble and so it cannot react with the stomach acid. It remains in the gut, passing along until it is excreted in the faeces.
Other barium salts, however, even if insoluble in water, may be dissolved in the stomach acid and then absorbed, causing poisoning and ultimately death. This happened in a number of fatal cases in the past, where barium thiosulphate was given in error for barium sulphate during an X-ray investigation, and barium carbonate, as a medicine for gastric problems, in error for bismuth carbonate.
Boron-containing compounds were once widely used as medicines. Borax – sodium borate – and boric acid were both used as disinfectants, because they had weak bacteriostatic and fungicidal activity. They were also used in mixtures for the treatment of epilepsy. However, boron compounds are toxic; a dose of 5g of boric acid is enough to make a person ill and 20g would put their life in danger. Details of a number of boron poisonings are given in the Household Horrors and Noxious Nursery chapters.
Migraine, gout and dropsy
Ergot is a fungal infection that grows on the cereal crop rye. In the past, people who unwittingly consumed bread made from flour of infected rye grain suffered a condition called ‘St. Anthony’s Fire’. The symptoms that they developed (described in Chapter 3) were due to the ergot alkaloids, produced by the fungus, infecting the grain. This fungus produces a large number of different ergot alkaloids, a dozen of which are chemically related to LSD.
Some of these alkaloids have been used medicinally, including ergotamine, which was used in medicine to treat migraine, and ergometrine which was used in childbirth. Today newer, more effective agents are increasingly used.
Ergotamine causes constriction of blood vessels and so relieves the spasm and subsequent overdilatation of certain arteries in the brain, which cause the throbbing recurrent headaches, usually one-sided, that we call migraine. The dose that can be taken is restricted, as overdose can lead to such drastic vasoconstriction that gangrene of the extremities, particularly of the toes, can occur.
Ergometrine acts specifically on the uterus, stimulating contractions during childbirth to assist labour, and also helping to control bleeding afterwards. Less than a milligram of this potent alkaloid is needed, and is usually given by injection.
Colchicine is a potent alkaloid derived from the meadow saffron corm, which is still used today in the treatment of gout. Precise instructions are required to be followed to prevent toxic side effects. The dose to treat an acute attack of gout is usually between three and six milligrams. No more than ten mg in total should be taken during each attack. A further course should not be taken within three days; such is the danger of toxicity. The tablets each contain 500 micrograms (half a milligram), and the dosage is to take one tablet every two to three hours until relief of pain is achieved, or until vomiting and/or diarrhoea occurs, these being the first signs of toxicity.
In the late 1960s, two women took, respectively, 26mg and 39mg of colchicine in suicide attempts and somehow survived. They suffered nausea, vomiting, colic and diarrhoea, followed by cardiovascular, neurological and dermatological signs of toxicity. Throughout, neither patient lost consciousness, and after many months of illness, they both eventually recovered.
About a hundred years ago, ‘Laville’s Gout Cure’, which contained both colchicine and quinine, could be bought from any pharmacy. The British Medical Journal reported a case in 1915 in which a patient took so much of this patent remedy over a period of 19 days that he became paralysed. This paralysis persisted for nearly a month, and even six months later the patient had still not fully recovered.
Digoxin is another potent medicine derived from a natural source, found in the leaves of the foxglove plant. The dose of digoxin, like colchicine, is measured in millionths of a gram. Digoxin intoxication was common years ago, before variations in bio-availability were properly understood in the pharmaceutical industry: Digitalis leaves collected in the late afternoon contain far higher levels of digoxin than leaves collected early in the morning, due to chemical changes happening in daylight.
Today digoxin tablets are standardised and available in three strengths: 62.5, 125 and 250 microgram. Patients starting to take digoxin always start on a low dose. The drug is introduced very carefully, with the patient’s digoxin level monitored at regular intervals, to ensure that the dose is optimal for that specific patient, as everybody is different.
Murder by chloroform
In the 19th century, chloroform was used as an anaesthetic. Today, small quantities are used as flavouring is some medicines because in very dilute aqueous solution it tastes far more pleasant than the often very bitter active ingredient, so making the medicine far more palatable.
Adelaide Bartlett was tried at the Old Bailey in 1886 on a charge of murdering her husband using chloroform. When she was 19, Adelaide had married Edwin Bartlett, a prosperous grocer who was ten years her senior. In 1885, Adelaide and Edwin became friendly with a young Wesleyan minister, the Reverend George Dyson. Edwin made a will, leaving everything to his wife and making the minister his executor.
Within a few weeks of making his will, Edwin became ill with a gastric complaint. He became an invalid and eventually died on New Year’s Day, 1886. On examination of his body, a large quantity of liquid chloroform was found in his stomach and Adelaide was charged with his murder. Try as they might, however, the prosecution were unable to explain how Adelaide had administered the chloroform, and she was acquitted. Nothing is known about what happened to her after the trial.
Opium and onwards
In the first half of the nineteenth century, opium was refined into morphine, codeine and papaverine, all highly addictive painkillers. Morphine was the most important of these alkaloids, and was named after Morpheus, the Greek God of Dreams.
Laudanum was the commonest painkiller available at this time; everybody used it and many became addicted to it. Laudanum was simply an alcoholic solution of opium, containing a mixture of more than 20 alkaloids that were to be found in raw opium.
Today morphine and other opioids are widely used to relieve pain, particularly for the terminally ill, by injection or as patches, tablets, capsules and oral solutions. Pain management at its best is now highly sophisticated because the hospice movement has pioneered major improvements in pain control. However, continuing research for similar, yet more powerful, painkillers is needed as, even today, some 20 per cent of terminal patients do not have complete pain control – some pain is still intractable, despite the best efforts of doctors and nurses.
Research for new and improved medicines is a continual process. Naturally occurring substances, many of which are poisonous, are being utilised in the search for more effective medicines to replace existing sub-optimal ones, as well as for medicines to treat those conditions for which there is as yet no suitable treatment. Tetrodotoxin, derived from a number of fish, such as the puffer fish, is far more poisonous than cyanide, and is currently being investigated for possible future use in medicine. Derivatives of tetrodotoxin have been found to be 3,000 times more powerful than morphine in the control of extreme pain by stopping the pain signals from reaching the brain.
Galantamine is an example of this more recent research. This substance was derived initially from snowdrop and daffodil bulbs, and is now in use in the treatment of Alzheimer’s disease. Supplies of the bulbs are being imported from Bulgaria and China; however, there are plans to plant some 30 to 40 acres of daffodil bulbs in the Black Mountains area of Wales to provide a homegrown supply of galantamine.
Botulinum toxin is now used in medicine, with minute quantities being injected to alleviate tics and spasms that arise from muscular overactivity. These work by paralysing the affected muscle. Botulinum toxin is probably best known to the general public as Botox, a beauty treatment for the temporary removal of wrinkles. Whatever the use, the injections need to be repeated every two or three months to maintain the effects.
Adulterated consequences
Over the years, a number of incidents have come to light where medicines have been adulterated with dire consequences. Unbelievably, ethylene glycol, perhaps better known as antifreeze, was found in Paracetamol Elixir, a children’s liquid painkiller on sale in Bangladesh in 1995. This caused an epidemic of poisoning in which some children died from kidney failure as a result. Ethylene glycol is sweet and cheaper than sugar – but deadly. Several such cases were described in Chapter 13.
Arsenic has been found in adulterated herbal preparations. This is an ongoing problem, common in the past, in some parts of the world and still causing problems in the twenty-first century, particularly in India and China. In 1975, some 74 cases were reported in Singapore. These cases resulted from the use of herbal preparations which were intended to treat asthma and other illnesses. Another report involved a man who had taken a proprietary asthma relief preparation, which contained arsenic, for 55 years – its continued use eventually resulted in a massive haemorrhage.
Also in the 1970s, a 59-year-old man died following the application to his face of an arsenical paste, which was sold to him as a quack cancer cure. While using this product, he developed arsenical peripheral neuropathy, with an acute respiratory involvement and chronic bronchitis. During the 1970s there were also a number of reports about arsenic trioxide being used in India as a supposedly aphrodisiac addition to opium.
And, unbelievable as it may seem, there is even an Ayurvedic medicine containing arsenic, which is commonly taken during pregnancy by women in some parts of India, in the hope of producing a male child.
In the latter part of the twentieth century, many instances of medicines containing heavy metals and other poisons came to light. Lead and mercury have been found in Indian ethnic medicines. Bal Jivan Chamco Baby Tonic was found to contain lead, as were many Chinese herbal medicines from Hong Kong. Ointments supplied to treat skin complaints, containing Chinese herbal remedies, have also been found to be adulterated with steroids.
A report in the Archives of Disease in Childhood in 2004 told of creams, purchased by parents, for use on children who attended a specialist skin clinic in Birmingham, UK. The parents had purchased a variety of Asian herbal creams because they were worried about the side effects of the prescribed steroids that their GPs or consultant dermatologists wished them to use, as prolonged use of steroid creams or ointments can cause skin thinning and growth retardation. The parents were very pleased with the results of using the supposed natural alternatives. However, analysis of the creams found that 20 out of 24 creams contained potent or very potent steroids, which were even stronger than those prescribed by the doctors. No wonder the results were so impressive.
Other Chinese herbal remedies were also found to be adulterated with western drugs so that their efficacy was greatly enhanced. Sometimes these remedies were toxic because a cheaper but poisonous herbal ingredient had been substituted in a mixture. Similar reports of toxicity due to the presence of arsenic and mercury as adulterants, in a variety of Indian ethnic remedies, were made in 1993.
Even in the 21st century, such practices continue. As many as one fifth of all Ayurvedic medicines imported from India have been found to contain arsenic, lead and other heavy metals. Sometimes these are accidental contaminants, but in other cases they are deliberately included, in the belief that they have health benefits, such as promoting vitality, rejuvenating energy levels and controlling blood sugar. Metals may be present due to the practice of rasa shastra by some practitioners, where herbs are combined with metals, minerals and even ground-up gemstones. Although Ayurvedic medicine has a long tradition of use in India – hundreds of years – there is little scientific evidence of its efficacy.
In the past, many substances we now recognise as poisons were used as medicines. As their toxic nature became known and more effective, safer drugs have been discovered and developed, and these poisons have thankfully fallen from use.