CHAPTER 1
THE HISTORY OF DRUGS
I wonder what's around the bend? said the explorer
I wonder what that plant is? said the collector
I wonder what's in it? said the chemist
I wonder what activity it has? said the pharmacologist
I wonder if it'll work in this case? said the physician
I hope she lives! said the father
Please God! said the mother
I think she'll be all right in the morning, said the nurse
– MARGARET KREIG Green Medicine
Ever since human beings first walked this earth they have searched for materials that would ease their suffering. As time went on they came to know which plants would feed their hunger, which would poison, and which would heal. In the ancient Sumerian town of Nippur, prescriptions were written on clay tablets and from these we know that over 4,000 years ago people used flowers, seeds, leaves, fruits, roots, and barks in their medicines. Among the plants they used were thyme, myrrh, and pine — which are still used today in the form of essential oils — and willow, the source of aspirin.
Aspirin is another name for acetyl-salicylic acid, a synthetic first produced in 1899 and derived from salicin, the active ingredient, named after salix — a family of willow tree. For thousands of years resins and juices from the bark and leaves of the willow have been used to treat rheumatism, neuralgia, and other ailments. The scientific history of the willow is traced to an 18th century clergyman, Edmund Stone, who had by recommendation or accident acquired the habit of chewing the bark. Interestingly, salicin is also a drug for the tree itself — conferring "systematic acquired resistance" on it, according to scientists at the Agricultural Biotechnology Research Unit of Ciba-Geigy, the multinational chemical company. Apparently, the willow trees use it to ward off infections, which they are prone to because they often grow by stagnant water.
Malaria has killed more people in this world than any other disease. The first drug treatment was quinine, which continues to be used against strains of the disease that are resistant to newer antimalarials, and is more commonly prescribed to prevent painful leg cramps at night. The source of this drug is the bark of a flowering evergreen, Cinchona, which grows on the Andean slopes of South America. The bark, first imported to Europe in 1645, was widely used as an antimalarial although its mysteries were not uncovered until 1819 when pharmaceutical chemists extracted one of the alkaloids and named it quinine after the Peruvian Indian word quina-quina, the "bark of barks."
As people explored their natural environment, they inevitably came across those plants that have an effect on the mind. So it was in India and Africa where for hundreds and perhaps thousands of years people used the root of related species of rauwolfia as a tranquilizer and treatment for "moon madness" — lunacy. In 1925 an eminent Nigerian living in London became psychotic but the doctors treating him couldn't help. The witchdoctor was summoned and arrived with his rauwolfia root — which did the trick. The active substances in rauwolfia (named after Leonhard Rauwolf, the 16th century physician and plant explorer) were isolated in the late 1940s by Indian scientists and after more work by the Swiss drug company, Ciba-Geigy, the first mind or mood altering drug based on rauwolfia alkaloids, reserpine, hit the market. And what a market it was — $80 million by the mid 1970s.
Not all alkaloids are so easy to reproduce chemically because they have large compounds which are difficult to synthesize. An example of this is the Madagas-can Periwinkle, the source of vincristine sulfate, an essential drug in any pharmacy dealing with childhood leukemia and certain lymphomas. It still takes 12 tons of crushed leaves to produce one ounce of the drug — also the source of Vinblastine, used to treat Hodgkin's disease. Over the years untold suffering has been alleviated by this innocent-looking pink and white ornamental, Catharanthus roseus, which gardeners appropriately call "bright eyes." Cancer treatment would be a harder task today without the 70% of antitumor drugs derived from native medicines.
Originally, all drugs were natural. The Ayurvedic system of medicine, thought to be at least 5,000 years old, is still extensively used in the Indian subcontinent and is studied by many Western medics as well. The text books mention 8,000 different natural medicines, using plant, animal, and mineral materials. Chinese herbal medicine is also becoming popular in the West, and of course continues to be of central importance in the materia medica of China. The first drug directory that we know of is the 2800 B.C. Pen Ts'ao, written by herbalist Shen Nung. In the Western tradition, credit for establishing medical botany as an applied science is given to the Greek physician Pedanios Dioscorides who in 78 A.D. published his Materia Medica, which detailed the properties of about 600 medicinal plants, as well as the medicinal value of certain animal products. Books such as these, recording the properties of natural products, were the mainstay of western medicine for about 1,400 years. The concept of medicinal chemistry was introduced in the 1520s by Paracelsus, a Swiss pharmacist-physician whose "real" name was Theophrastus Bombastus von Hohenheim. Paracelsus advocated the use of mineral salts and acids and experimented with various chemical processes including distillation. It would be another three hundred years before medical chemistry really took off, however, inspired by the German apothecary's assistant Friedrich Serturner, who in 1806 isolated the first active alkaloid of a natural drug — raw opium from the poppy Papaver somniferum. Serturner named it morphine after Morpheus, the Greek god of Dreams. Codeine is a derivative of morphine.
The history of drugs clearly shows the source of inspiration — nature. However, nature has its disadvantages. Imagine yourself the manager of a drug company looking at your storehouse full of bags of herbs, barks, roots, leaves, and flowers imported from all over...
