Drugs, Pills, and Witchcraft.. Oh My!

Wonder Drugs

Bayer Aspirin

     Edward Jenner demonstrated the production of an artificial immunity to disease for smallpox in 1798. Felix Hofmann, from the Bayer company, began investigating compounds related to salicylic acid in 1893. Salicylic acid can be produced from the flower of meadow-sweet, Spiraea ulmaria, and it is used to reduce fever and inflammation. However, it irritates the lining of the stomach, making it less valuable as medicine. Hofmann gave acetyl salicylic acid to his father, who had rheumatoid arthritis. This derivative of salicylic acid has an acetyl group instead of an OH group. In 1899, Bayer marketed packets of "aspirin" in the powdered form. The name comes from the combination of acetyl and Spiraea ulmaria. Aspirin has become the most popularly used drug for illness and injuries, with over 40 million pounds being produced every year in the United States.
     Paul Ehrlich had a theory that if one microorganism absorbed a dye while another did not, then a toxic dye could kill only the tissue that absorbs it, leaving the other tissue damage-free. He was searching for his "magic bullet", as he called it, and it was a dye that would target the tissue that absorbed it. After testing 605 chemicals, Ehrlich found a safe and reasonable compound in 1909. "Number 606", as it was called, was an aromatic compound that contained arsenic, and worked at targeting the spirochete that causes syphilis. The following year, Hoechst Dyeworks marketed this compound with the name "salvarsan". In the 1930s, Gerhard Dogmak used protonsil red to treat his daughter, who had a major streptococcal infection. The dye was effective because, in the body, protonsil red breaks down into sulfanilamide, which has been created in various forms between 1935 and 1946. These molecules, known as sulfa drugs, are active against bacterial infection, but they are not technically antibiotics. Antibiotics originate from microbes, while sulfanilamides are man made. However, the term antibiotic has come to describe any substance that kills bacteria.
     Louis Pasteur was able to show that a microorganism could be used to kill another in 1877. In 1928, Alexander Fleming was studying staphylococci bacteria, when he found that mold had contaminated his cultures. This mold was from the Penicillium family, and it became transparent and disintegrated. Fleming performed tests, and his results showed that the mold produced a compound that was antibiotic toward the staphylococcus batceria. However, the first clinical trial for penicillin was not until 1941. By 1943, pharmaceutical companies in America were producing approximately 800 million units of penicillin. In 1944, monthly production of the antibiotic was over 130 billion units. The structure of penicillin was unknown until 1946, and synthetic penicillin was only produced in 1957.

The Pill

     A contraceptive molecule, norethindrone, had a major role in society upon its emergence in 1960. "The pill" as it was known, was the first oral contraceptive. It is a steroid, but not in the sense of athletic performance enhancers. The first isolation of testosterone occurred in 1935 from ground up bull testes. The first isolation of a sex hormone was that of estrone in 1929 from the urine of pregnant women. The difference between male and female sexual characteristics lies in the molecular structure of the hormones. Female characteristics will become evident if the hormone has one less CH3, an OH instead of a double bonded O, and more carbon double bonds. Progesterone suppresses further ovulation when a woman is pregnant, so chemical contraception was based off an outside source of progesterone. However, natural progesterone has to be injected because it reacts with stomach acids, and finding sufficient amounts of progesterone in animals is difficult. Artificial progesterone that could be taken orally was synthesized.

Marker's process of isolating steroid system

     Russell Marker intended to develop an affordable way to produce cortisone. He knew that various plants consisted of compounds containing steroids, and there were more of them than in animals. Marker began working with the sarsasaponin molecule, a saponin that is found in the sarsaparilla vine. When the three sugars are removed from the molecule, a sarsasapogenin is left behind. Marker isolated the steroid system from the sarsasapogenin, and the addition of a few steps to this process allowed the development of synthetic progesterone. Although he destroyed his laboratory notes and experiments in an attempt to remove his name from the field of chemistry in 1949, Marker's work is known for making birth control pills possible.
     Carl Djerassi used the Marker degradation to demonstrate that cortisone could be produced from diosgenin, then syntheszed estrone and estradiol from diosgenin as well. He wanted to produce an artificial progestin, which would have similar properites as progesterone but could be taken orally. The pill was designed for women who had a history of miscarriage, not to be used as a contraceptive pill. In 1951, Djerassi and his team patented norethindrone, a molecule that was eight times more powerful than progesterone.
     Margaret Sanger was arrested for providing contraceptives to immigrant women in 1917. Katherine McCormick helped Sanger smuggle illegal contraceptives into the United States, and also provided financial support for the birth control cause. Gregory Pincus was challenged to find a contraceptive that worked perfectly, and found that norethynodrel (later called Enovid) fit the requirements. He tested this molecule and saw that it worked 100 percent effectively to prevent ovulation. The field trials for the molecule were held in Puerto Rico, and out of more than 2,000 volunteers, the failure rate was only one percent. Although it is much easier to prevent ovulation of a monthly egg than production of millions of sperm on a daily basis, molecules are being investigated as a possible birth control pill for men.

Molecules of Witchcraft

     In the middle of the 14th century, any magic that was performed outside the church was considered to be Satan's work. Witches were believed to be in a pact with the devil, and by the middle of the 15th century, traditional rules of law no longer applied to the trials of witches. Accusations were considered evidence, and torture was a routine occurrence. Many accused "witches" were women who were herbalists, who used plants to heal and provide relief. William Withering used foxglove extracts to treat congestive heart failure in 1795. These cardiac glycosides can reduce heart rate, and regulate and strengthen the heart beat. Alkaloids are plant compounds that contain nitrogen, affect the human central nervous system, and they are typically very toxic. "Flying salves" were ointments that were believed to promote flight, and they were made from plant extracts such as mandrake, belladonna, and henbane. The alkaloids present in the extracts are not water soluble, so they would be dissolved in fat or oil and applied as an ointment.

Visual effects of LSD

     In any disaster, the blame was placed on elderly women. They were easy targets because they could no longer have children and they may not have had any family support. These women often lived on the outskirts of town, and lived in extreme poverty, relying on their herbalist skills. These qualities made them susceptible to the accusations of witchcraft. Ergot poisoning had a drastic effect on populations, as the grains would become infected with the fungus. It is believed that ergotism had something to do with the beginning of the Salem witch trials in Massachusetts. Young people are more vulnerable to infection, and the first "bewitched" victims were girls and young women.
     In 1938, Albert Hofmann created his 25th derivative- lysergic acid diethylamide LSD-25. Nothing appeared to be exceptional about the molecule's properties. However, in 1943, Hofmann again created this derivative (LSD) and unintentionally experienced the first "acid trip". Since LSD cannot be absorbed through the skin, Hofmann was believed to have transferred it from his fingers to his mouth. The Sandoz company marketed LSD as a psychotherapy tool in 1947. In the 1960s, it became a very popular drug for people worldwide.