III. TECHNOLOGY MILESTONES IN HEALTH AND MEDICINE Chemistry has contributed many of the life-saving breakthroughs in health and medicine that allow us to live longer, happier, and healthier. Throughout much of human history, medicine and health care was primitive. If people became sick or injured, doctors could do little more than comfort them and keep them clean. The last 100 years have revolutionized the way in which doctors heal patients by curing disease, repairing injuries, and even preventing health problems before they occur. Hard- working chemists and chemical engineers have helped to found modern medicine by developing novel pharmaceuticals, creating new medical equipment, and refining diagnostic procedures. Millions of human lives have been saved and improved by the health and medical advances developed through chemistry. III.1. Pain and Inflammation Management Morphine Aspirin Cortisone III.2. Psychotherapeutic Agents Chlorpromazine Tricyclic antidepressants Benzodiazepines III.3. Hormones and Hormone Regulators Insulin Testosterone Progestins, estrogens, and oral contraceptives III.4. Gastro-intestinal Agents Evolution of ulcer therapy III.5. Medical Testing and Disease Diagnostics Medical imaging technologies Medical isotopes Development of chemical assays Evolution of personal monitoring III.6. Anti-infective Drugs Salvarsan and Prontosil Penicillin Zidovudine (AZT) III.7. Cardiovascular Management Regulating heart beat Treating heart failure Affecting blood clots Controlling blood cholesterol levels III.8. Cancer Chemotherapy Evolution of cancer chemotherapy Cytotoxic drugs Tamoxifen III.9. Novel Healthcare Materials Artificial limbs and medical devices Medical equipment Disinfectants and bleach Chronology

1899 Aspirin is manufactured to fight pain, joint inflammation and swelling Salvarsan is the first major chemotherapeutic agent to be made Insulin is used to alleviate high blood sugar associated with diabetes 1923 The chemical structure of morphine is determined Pregnancy test developed to detect estrogens in urine Prontosil cures the deadly streptococcal infection Nitrogen mustards begin the age of cancer chemotherapy Penicillin fights infection and inaugurates antibiotic therapy Digoxin is approved to treat thrombotic diseases (blod clot formation) Chlorpromazine begins modern antipsychotic therapy Enovid is manufactured and enters to market as an oral contraceptive Herbal cytotoxic drugs are used to fight cancer Tagamet inhibits acid secretion in stomach during treatment of gastric ulcers Tamoxifen introduces hormone blockers in cancer chemotherapy Zidovudine (AZT) is approved by FDAfor treatment of HIV infection. Technology Milestones in Health and Medicine Chronology

III.1. Pain and Inflammation Management Morphine Used from the early 1800s to decrease the sensation of pain, morphine was extracted from raw opium. The Hungarian pharmacist Janos Kabay revolutionized morphine production in the 1920s : by extracting it not only from the immature poppy-head but from the dry poppy-straw. It was studied in 1923 to determine its chemical structure in an effort to synthetize a potent analgesic free from undesirable properties such as addiction and respiratory depression. Understanding exactly how the naturally-occurring extract worked in the human body allowed a synthetic version of morphine to be developed and subsequent, safer drugs to be created, such as nalorphine and naloxone in The thomb of Janos Kabay in Budapest, Hungary

III.1. Pain and Inflammation Management Aspirin In 1890, salicylic acid was being manufactured as a cheap and effective inflammation reliever for rheumatoid arthritis despite unpleasant side effects (nausea, gastric catarrh). Acetylsalicylic acid (or aspirin) was synthesized in 1897 by the German chemist Felix Hoffmann at Bayer and tested pharmacologically by Heinrich Dreser. Production started in 1899 and first pills were sold in Aspirin soon became popular because it had fewer side-effects than salicylic acid. Aspirin, the first medicine to be produced at industrial level, is still manufactured in large quantities today. Aspirin was consumed mainly as an anti-headache drug until the mid-eighties when its beneficial effects in preventing heart attacks were discovered Aspirin, the first pills manufactured ever (1900) Acetylsalicylic acid

III.1. Pain and Inflammation Management Cortisone In the 1940s, studies of the adrenal gland cortex in the 1940s identified that certain naturally-occurring hormones (also called steroids) have anti- inflammatory properties. First isolated from its natural source in 1936, cortisone was synthesized by the American Lewis Hastings Sarett in It was already being commercially manufactured in the next year du to its miraculous activity in rheumatoid arthritis. Subsequent clinical studies showed that it did not cure arthritis, triggered serious side effects, but enjoyed additional uses in asthma and allergy treatments. Further studies of steroid synthesis led to the creation of prednisone, prednisolone, and dexamethasone as better anti- inflammatory agents with reduced side effects. Lewis Hastings Sarett Deformity induced by joint inflammation

III.2. Psychotherapeutic Agents Chlorpromazine Chlorpromazine (Thorazine, Hibernal) was first used to treat schizophrenia in 1954 after its original creation as an antihistamine anti-allergic. This new therapy proved itself dramatically and heralded the modern era of antipsychotic therapy, and became a reference of the central nervous system drugs. Controlling mental illness through medication soon supplanted earlier treatment methods, such as electroshock, insulin shock, prefrontal lobotomy (a surgical treatment disconnecting prefrontal hemispheres), and helped to decrease the rate of institutionalization worldwide. Later research shed light on the pharmacological mechanism of chlorpromazine and served as a basis for the development of many other anti- psychotic drugs such as haloperidol and olanzapine. Pictures from the film: One Flew Over the Cucoo’s Nest (1975), which portrays the disastrous effect of mental illness.

III.2. Psychotherapeutic Agents Tricyclic antidepressants In 1958, a clinical study of imipramine, a drug which was originally developed as an antipsychotic, revealed its antidepressant properties. It functions therapeutically by affecting the activity of neurotransmitters (stimulus transmitting agents) in the brain. The many subsequent drugs that were developed in this class became collectively known as `tricyclic’ antidepressants. Tricyclic antidepressants become the standard of therapy for this disease. The onset of depression following labour The more the sunshine the less the depression

III.2. Psychotherapeutic Agents Benzodiazepines In 1959, chlordiazepoxide (Librium) launched a potent new class of anti-anxiety agents, the benzodiazepines. This drug and its subsequent derivatives rapidly replaced barbiturates and Meprobamate, an earlier moderately successful anxiolytic agent discovered in 1950, and are considered to be some of the most successful drugs of this era. The highly tolerable and safe benzodiazepines also prove successful as hypnotic agents, muscle relaxants, and treatment of for epilepsy.

III.3. Hormones and Hormone Regulators Insulin Insulin, a protein hormone produced by special cells of the pancreas, controls the level of blood sugar (glucose) in the blood. Lack of insulin leads to the development a fatal disease, diabetes type I. Two young Canadian doctors, Frederick Banting and Charles H. Best isolated and purified a new injectable extract from bovine pancreas in Their first patient was a dying 14- year-old boy, who was released from the hospital after a few weeks. Insulin was manufactured from bovine pancreas by Eli Lilly and Company in The first insulin engineered from human sources using recombinant DNA technology was produced in Frederick Banting and Charles H. Best, the inventors of insulin

III.3. Hormones and Hormone Regulators Testosterone Testosterone is responsible for the development of the male sex organs and secondary sexual characteristics. It is a steroid hormone, structurally similar to cholesterol. Testosterone was first synthesized from cholesterol in 1935 to treat hormone deficiency diseases. Testosterone can be manufactured by chemical and microbiological modification of readily available naturally-occurring materials.