Penny le Couteur & Jay Burreson (38 page)

The mania affected Catholic and Protestant countries alike. At the height of witch-hunt paranoia, from about 1500 to 1650, there were almost no women left alive in some Swiss villages. In regions of Germany there were some small villages where the whole population was burned at the stake. But in England and in Holland the witch craze never became as entrenched as in other parts of Europe. Torture was not allowed under English law, although suspected witches were subjected to the water test. Trussed and thrown into a pond, a true witch floated, to be retrieved and properly punished—by hanging. If the accused sank and drowned, she was considered to have been innocent of the charge of witchcraft—a comfort to the family but little use to the victim herself.

A Delft tile from the Netherlands (first part of the eighteenth century) showing a witch trial. The accused on the right, only her legs visible above the water, is sinking and would be proclaimed innocent. Satan's hand can be seen supporting the accused woman floating to the left, who—her guilt now proven—would be pulled from the water to be burned alive at the stake.
(Courtesy of the Horvath Collection, Vancouver)

The witch-hunt terror faded only slowly. But with so many people accused, economic well-being was threatened. As feudalism retreated and the Age of Enlightenment dawned, as the voices of brave men and women who themselves risked the gallows and the stake to oppose the madness became louder, the mania that had swept Europe for centuries gradually abated. In the Netherlands the last execution of a witch took place in 1610 and in England in 1685. The last witches executed in Scandinavia—eighty-five elderly women burned at the stake in 1699—were convicted solely on the basis of statements from young children who claimed to have flown with the women to sabbats.

By the eighteenth century, execution for witchcraft officially ceased: for Scotland in 1727, France in 1745, Germany in 1775, Switzerland in 1782, and Poland in 1793. But although the Church and the state no longer executed witches, the court of public opinion was less ready to give up the fear and loathing of witchcraft acquired by centuries of persecution. In more remote rural communities old beliefs still held sway, and many a suspected witch met a nasty, if unofficial, fate.

Many of the women accused of witchcraft were herbalists, skilled in the use of local plants to cure disease and provide relief from pain. Often they could also be relied upon to supply love potions, to cast spells, and to remove hexes. That some of their herbs did have healing powers would have seemed as magical as the incantations and rituals surrounding the rest of the ceremonies they would perform.

Using and prescribing herbal medicines would have been then—as it is now—a risky business. Different parts of a plant contain varying levels of effective compounds; plants gathered from different locations can vary in their ability to cure; and different times of the year can change the amount of a plant needed to produce an appropriate dose. Many plants in an elixir might be of little benefit, while others might contain medications that would be extremely effective but also deadly poisonous. The molecules in these plants could enhance the reputation of an herbalist as a sorcerer, but the very success of these molecules might eventually prove deadly for these women. Those herbalists whose healing skills were the greatest might be first to be branded a witch.

Salicylic acid, from the willow tree and the meadowsweet plant common throughout Europe, was known centuries before Bayer and Company began marketing aspirin in 1899 (see Chapter 10). The root of wild celery was prescribed to prevent muscle cramps, parsley was believed to induce a miscarriage, and ivy was used to relieve symptoms of asthma. Digitalis, an extract from the common foxglove
Digitalis purpurea,
contains molecules that have long been known to have a powerful effect on the heart—the
cardiac glycosides.
These molecules reduce the heart rate, regularize heart rhythm, and strengthen heartbeat, a potent combination in inexperienced hands. (They are also saponins, very similar to those found in sarsaparilla plants and wild Mexican yams from which the birth control pill norethindrone was synthesized; see Chapter 11.) An example of a cardiac glycoside is the digoxin molecule, one of the most widely prescribed drugs in the United States and a good example of a pharmaceutical based on folk medicine.

In 1795 a British physician named William Withering used extracts of foxglove to treat congestive heart failure after hearing rumors of the plant's curative abilities. But it was well over a century before chemists were able to isolate the molecules responsible.

In the
Digitalis
extract there are other very similar molecules to digoxin; for example the digitoxin molecule, which lacks only the OH, as indicated in the structure drawing. Similar cardiac glycoside molecules are found in other plants, usually members of the lily and ranunculus families, but foxglove is still the main source for today's drug. Herbalists have had little difficulty finding heart tonic plants in their own gardens and in local meadows. Ancient Egyptians and Romans used an extract from the sea onion, a member of the hyacinth family, as a heart tonic and (in larger doses) as a rat poison. We now know that this sea onion also contains a different cardiac glycoside molecule.

These molecules all have the same structural feature, which is therefore likely to be responsible for the cardiac effect. All have a five-membered lactone ring attached to the end of the steroid system and an extra OH between the C and D rings of the steroid system, as shown here:

Molecules that affect the heart are not found only in plants. Toxic compounds that are similar in structure to the cardiac glycosides are found in animals. These molecules do not contain sugars, nor are they used as heart stimulants. Rather, they are convulsive poisons and of little medical value. The source of these venoms is amphibians; extracts from toads and frogs have been used as arrow poisons in many parts of the world. Interestingly, the toad is, after the cat, the most common animal attributed in folklore as a familiar to a witch. Many potions prepared by so-called witches were said to contain parts of toads. The molecule
bufotoxin
is the active component of the venom of the common European toad,
Bufo vulgaris,
and is one of the most toxic molecules known. Its structure shows a striking similarity at the steroid ring system to the digitoxin molecule, with the same extra OH between the C and D rings and a six-membered, instead of five-membered, lactone ring.

Bufotoxin, however, is a cardiac poison rather than a cardiac restorative. Between the cardiac glycosides of foxglove and venoms from toad, supposed witches had access to a potent arsenal of toxic compounds.

In addition to their penchant for toads, one of the most abiding myths about witches is that they were able to fly, often on broomsticks, to attend a sabbat—a midnight tryst, supposedly an orgiastic parody of the Christian mass. Many accused witches confessed, under torture, to flying to such sabbats. This is not surprising—we too would probably make such a confession if we were subject to the same horrific agonies perpetrated in the search for truth. The surprising thing is that a number of accused witches confessed,
before
torture, to the impossible feat of flying to a sabbat on a broomstick. As such a confession would not likely have helped these victims escape torture, it is quite possible that these women truly believed they had flown up the chimney on a broomstick and indulged in all sorts of sexual perversions. There may be a very good chemical explanation for their belief—a group of compounds known as alkaloids.

Alkaloids are plant compounds that have one or more nitrogen atoms, usually as part of a ring of carbon atoms. We have already met a few alkaloid molecules—piperine in pepper, capsaicin in chili peppers, indigo, penicillin, and folic acid. It can be argued that, as a group, alkaloids have had a larger effect on the course of human history than have any other family of chemicals. Alkaloids are often physiologically active in humans, usually affecting the central nervous system, and are generally highly toxic. Some of these naturally occurring compounds have been used as medicines for thousands of years. Derivatives made from alkaloids form the basis of a number of our modern pharmaceuticals, such as the pain-relieving molecule codeine, the local anesthetic benzocaine, and chloroquine, an antimalarial agent

We have already mentioned the role that chemical substances play in protecting plants. Plants cannot run away from danger and cannot hide at the first sign of a predator; physical means of protection such as thorns do not always stop determined grazers. Chemicals are a passive but very effective form of protection from animals as well as fungi, bacteria, and viruses. Alkaloids are natural fungicides, insecticides, and pesticides. It has been estimated that, on average, each of us ingests about a gram and a half of natural pesticide every day, from the plants and plant products in our diet. The estimate for residues from synthetic pesticides is around 0.15 milligrams daily—about ten thousand times less than the natural dose!

In small amounts the physiological effects of alkaloids are often welcomed by humans. Many have been used medicinally for centuries. Acrecaidine, an alkaloid found in betel nuts from the betel palm,
Areca catechu,
has a long history of use in Africa and the East as a stimulant. Crushed betel nuts are wrapped in the betel palm leaves and chewed. Betel users are easily recognized by their characteristic dark-stained teeth and by their habit of spitting copious amounts of dark red saliva. Ephedrine, from
Ephedra sinica
or the ma huang plant, has been used in Chinese herbal medicine for thousands of years and is now used in the West as a decongestant and bronchodilator. Members of the vitamin B family, such as thiamine (B
₁
), riboflavin (B
₂
), and niacin (B
₄
), are all classed as alkaloids. Reserpine, used in the treatment of high blood pressure and as a tranquilizer, is isolated from the Indian snakeroot plant,
Rauwolfia serpentina.