History of Pharmaceuticals
Feverish and tossing, the child lies on the bed in the darkened room. The family gathers, tearful but resigned. The doctor sits at the patient's bedside, helpless, as the child slips away.
The scene, from Louisa May Alcott's Little Women, depicts the death of young Beth from scarlet fever. But in the late 1800s, similar scenes were played over and over again in real life: in the gilded mansions of the rich, in the sod homes on the prairie, in the teeming tenements of the immigrant-packed cities. Although the diseases varied - diphtheria, typhus, typhoid, cholera, and others - the denouement was almost always the same: death. But, though it would provide little comfort to the victims of disease and their families, hope - in the form of medical progress - was waiting in the wings.
As the 20th century dawned, disease cast a long shadow. A child born in 1900 could expect to live an average of 47 years, and infectious diseases took many children before they reached their teens. As Roy Porter wrote in The Greatest Benefits to Mankind, A Medical History of Humanity:
"Throughout the 19th century, and well into the twentieth, patients were besieged by infections, commonly lethal to old and young alike - diphtheria, chickenpox, scarlet fever, rubella and a multitude of gastro- intestinal and dysenteric troubles claimed millions of infants. Being a family doctor in 1830 and even a century later meant being called out late at night to febrile patients, sweating copiously and hectic in their breathing, suffering from some infant fever or from pneumonia (called the "old man's friend" because it was often speedily fatal). Measles and the other epidemic diseases of childhood were still killers; tuberculosis, syphilis, diphtheria, meningitis, and post-partum sepsis were widely encountered. "
In 1900, pneumonia and influenza were the leading causes of death in the United States, followed by tuberculosis and diarrhea. Heart disease - which tops the chart today - was only fifth; possibly because infectious diseases carried many people off before they grew old enough to develop heart disease.
Physicians had few weapons in their black leather bags to fight disease. The pharmacopoeia of time included drugs such as mercury for syphilis and ringworm, digitalis and amyl nitrate for the heart, quinine for malaria, colchicum for gout, and plant-based purgatives.
The Germ Theory
In the second half of the 19th century, scientists such as Louis Pasteur and Robert Koch laid the ground work for a revolutionary theory: specific micro-organisms, or germs, cause disease. Pasteur learned that some cultures of bacteria lose their lethal character and become attenuated. Knowledge that led him to vaccinate with attenuated rabies microbes a nine-year old boy who had been bitten by a rabid dog. The boy survived unharmed. On Christmas day 1891, Emil von Behrig successfully treated a sick child with diphtheria antitoxin, signaling the eventual end of this disease.
In 1894, a young chemist name Felix Hoffman joined the pharmaceutical division of the German medical company Bayer and began searching for compounds to ease the pain of is arthritic father. He came upon salicylic acid, originally derived from willow bark, and made a chemical derivative to reduce the gastric distress it caused, tested it, and developed a commercial method of producing it. The result was aspirin.
In 1910, German bacteriologists Paul Ehrlich formulated the first "magic bullet", an arsenic compound effective against syphilis. The medicine, called Salvarsan, was developed and marketed by a German pharmaceutical and chemical company.
The Role of Pharmaceutical Companies
As discoveries were made, pharmaceutical companies rose to the task of developing these compounds, ensuring safety and efficacy and mass-producing and marketing the medicines. This is well illustrated by the discovery and development of insulin.
Diabetes mellitus is caused by a malfunctioning pancreas, which fails to produce insulin, the hormone that regulates blood sugar. For most of human history, diabetes meant death. In the late 19th century, scientists figured out the relationship of the pancreas to diabetes and attempted to isolate the hormone. All experiments failed until 1921, when Canadian physician Frederick Banting isolated the hormone. A U.S. based company, which had a research affiliation with the University of Toronto where Banting did his research, won the right to manufacture the drug. Overcoming technical problems, Lilly perfected methods of large-scale collection of raw material extraction, purification, and mass production. Introduced insulin commercially in 1923 and, within a few years, enough insulin was being produced to meet the needs of diabetes patients around the world.
Vaccines began to be commercially produced in World War I, and, together with rising living standards, helped curb some infectious diseases. But the major onslaught against infection began in the late 1920s, when the German chemical giant I.G. Farben hired a young scientist named Gerhard Domagk. In 1933, experimenting with dyes, Domagk found that an orange-red dye called Prontosil killed bacteria in mice. A few weeks later, the substance saved the life of a baby dying of a blood stream staph infection. Called "sulfur drugs" after the active ingredient in the dye, these medicines were found to halt the growth and proliferation of bacteria while the body's natural defense fought off the infection.
The Magic Mold
Penicillin, the great break through against infection of the 20th century, had actually been discovered - but not developed - in 1928. Returning from vacation, Dr. Alexander Fleming, a bacteriologist at London's St. Mary's Hospital, found that a mysterious mold has sprouted in a petri dish. Bacteria covered the entire dish - except where the mold was. Fleming noted the mold's anti-bacterial action and named it penicillin, but failed to develop it. In 1940, Oxford University scientists Howard Florey and Ernest Chain developed penicillin into a therapeutic agent, but in 1941, could not produce enough of the compound to cure a policeman with severe septicemia. The patient improved when the drug was administered, but died when the meager supply was exhausted. By 1943, several U.S. based pharmaceutical companies were mass-producing purified penicillin. By 1944, sufficient penicillin was available to treat all severe battle wounds suffered by U.S. troops in the D-Day battles. In the 1950s, known as the decade of antibiotics, new breakthroughs - to treat tuberculosis and other infections - followed swiftly.
Progress Against Cancer
Cancer has been known and studied since antiquity, but in the words of one scholar: " Before the twentieth century, the main institutions dealing with cancer were hospitals to die in."
Early hopes for treating cancer focused on the mustard gas used in the First World War, the first chemotherapy agent for cancer. Unfortunately, the gas killed healthy cells as well as cancer cells and at best delayed death for a short time. Similarly, children with leukemia were treated with cortisone drugs which prolonged remissions for only a short time. In 1948 Lederic Laboratories developed methotrexate one of the earliest anticancer agents and an anti-metabolite that destroys cancer cells. George Hitchings and Gertrude Elion developed anti-metabolites for scule leukemia in the late 1940s and early 1950s, while working at the Burroughs Wellcome Co.
This and other early work formed the basis for the remarkable progress made against cancer in recent decades. According to the National Cancer Institute for, deaths from all cancers combined (as well as for the top 10 cancer sites) declined in the United States between 1990 and 1997, and eight out of ten children now survive leukemia. Said John R. Selfrin, Ph.D., CFO of the American Cancer Society: "Cancer death rates have been falling since 1991, and since 1995 that decline has been even more rapid. This gives us great hope that in the new millennium, our dreams of conquering cancer are closer than ever to becoming a reality."
A March 2001 survey by the Pharmaceutical Research and Manufactures of America PhRMA) found 402 new medicines in development for cancer.
The #1 Killer - Heart Disease
Heart disease has topped the list of killer diseases of Americans for decades, but thanks in large part to new medicines, deaths from heart disease have been cut by more than half since 1950.
The first known heart medicine was discovered in an English garden in 1799, when physician John Ferriar noted the effect of dried leaves of the common foxglove plant, Digitalis Purpuro on heart action. Still used in heart medications, digitalis slows the force of the heart contractions and increases the amount of blood pumped per heartbeat. In 1867, nitroglycerin, a key ingredient of dynamite, joined the armamentarium against heart disease, to relieve angina. In 1901, drug company and university scientists isolated adrenaline from the glands of cattle and used it in medicines to stimulate the heart.
Until relatively recently, however, there were few medicines to treat some of the underlying causes of heart disease, such as high blood pressure and high cholesterol. When President Franklin D. Roosevelt developed high blood pressure in the early 1940s, all his doctors prescribed were sedatives and a low-salt diet. In 1949 Indian physician Roston Jal Vakil wrote a British medical journal about using the powdered root of the tropical plant Rauwolfia sepentina to lower blood. Three years later, drug company chemists isolated the active ingredient of the plant and made the drug resezione for high blood pressure.
The first diuretic to treat high blood pressure was approved in 1950. The first clinically used beta-blocker appeared in 1967. The first ACE inhibitor and the first calcium channel blocker were approved in 1981.
In the early 1970s, drug company scientists looking for a drug for a poultry disease discovered an organism that inhibits an enzyme required for the synthesis of one of the building blocks of cholesterol. This serendipitous discovery led to a new class of drugs called sratins, which can cut the risk of coronary death by more than 40 percent. Clot-dissolving drugs, pioneered in the 1980s, can actually stop heart attacks in mid-stream before permanent damage to the heart is done.
Despite the progress, nearly 61 million Americans - more than one in five - suffer from at least one type of cardiovascular disease, and nearly a million Americans a year die of these diseases - more than 2,600 every day. Pharmaceutical companies are currently developing 122 new medicines for cardiovascular diseases, many of which use 21st century technologies.
The American Heart Association projects that if all major forms of heart and blood vessel disease were eliminated, U.S. life expectancy would rise by almost seen years and the economic savings would total more than $300 billion a year. Cardiovascular disease claimed about 950,000 lives in the U.S. in 1998, which is 40.6 percent of all deaths.
Conclusion
In the past 100 years, pharmaceutical research has helped transform health care from a largely palliative practice to a science-based endeavor. Due in part to this transformation and in part to improvements in sanitation, average life expectancy in the U.S. has increased from 47 years in 1900 to more that 76.5 years today.
In addition to longer lives, pharmaceutical progress has brought better lives to millions of people. It has consigned many infectious scourges of the past to history books; it has transformed mental illness from a misunderstood cause of shame and fear into a highly treatable condition. It has helped make old age a time of active independence, rather than disability, for many. It has made impressive inroads against cancer, heat disease, stroke, and many other diseases.
As the 21st century begins, pharmaceutical companies are continuing the battle against humankind's ancient enemies and meeting new challenges, including seeking better treatments and cures for AIDS and Alzheimer's disease.
The scene, from Louisa May Alcott's Little Women, depicts the death of young Beth from scarlet fever. But in the late 1800s, similar scenes were played over and over again in real life: in the gilded mansions of the rich, in the sod homes on the prairie, in the teeming tenements of the immigrant-packed cities. Although the diseases varied - diphtheria, typhus, typhoid, cholera, and others - the denouement was almost always the same: death. But, though it would provide little comfort to the victims of disease and their families, hope - in the form of medical progress - was waiting in the wings.
As the 20th century dawned, disease cast a long shadow. A child born in 1900 could expect to live an average of 47 years, and infectious diseases took many children before they reached their teens. As Roy Porter wrote in The Greatest Benefits to Mankind, A Medical History of Humanity:
"Throughout the 19th century, and well into the twentieth, patients were besieged by infections, commonly lethal to old and young alike - diphtheria, chickenpox, scarlet fever, rubella and a multitude of gastro- intestinal and dysenteric troubles claimed millions of infants. Being a family doctor in 1830 and even a century later meant being called out late at night to febrile patients, sweating copiously and hectic in their breathing, suffering from some infant fever or from pneumonia (called the "old man's friend" because it was often speedily fatal). Measles and the other epidemic diseases of childhood were still killers; tuberculosis, syphilis, diphtheria, meningitis, and post-partum sepsis were widely encountered. "
In 1900, pneumonia and influenza were the leading causes of death in the United States, followed by tuberculosis and diarrhea. Heart disease - which tops the chart today - was only fifth; possibly because infectious diseases carried many people off before they grew old enough to develop heart disease.
Physicians had few weapons in their black leather bags to fight disease. The pharmacopoeia of time included drugs such as mercury for syphilis and ringworm, digitalis and amyl nitrate for the heart, quinine for malaria, colchicum for gout, and plant-based purgatives.
The Germ Theory
In the second half of the 19th century, scientists such as Louis Pasteur and Robert Koch laid the ground work for a revolutionary theory: specific micro-organisms, or germs, cause disease. Pasteur learned that some cultures of bacteria lose their lethal character and become attenuated. Knowledge that led him to vaccinate with attenuated rabies microbes a nine-year old boy who had been bitten by a rabid dog. The boy survived unharmed. On Christmas day 1891, Emil von Behrig successfully treated a sick child with diphtheria antitoxin, signaling the eventual end of this disease.
In 1894, a young chemist name Felix Hoffman joined the pharmaceutical division of the German medical company Bayer and began searching for compounds to ease the pain of is arthritic father. He came upon salicylic acid, originally derived from willow bark, and made a chemical derivative to reduce the gastric distress it caused, tested it, and developed a commercial method of producing it. The result was aspirin.
In 1910, German bacteriologists Paul Ehrlich formulated the first "magic bullet", an arsenic compound effective against syphilis. The medicine, called Salvarsan, was developed and marketed by a German pharmaceutical and chemical company.
The Role of Pharmaceutical Companies
As discoveries were made, pharmaceutical companies rose to the task of developing these compounds, ensuring safety and efficacy and mass-producing and marketing the medicines. This is well illustrated by the discovery and development of insulin.
Diabetes mellitus is caused by a malfunctioning pancreas, which fails to produce insulin, the hormone that regulates blood sugar. For most of human history, diabetes meant death. In the late 19th century, scientists figured out the relationship of the pancreas to diabetes and attempted to isolate the hormone. All experiments failed until 1921, when Canadian physician Frederick Banting isolated the hormone. A U.S. based company, which had a research affiliation with the University of Toronto where Banting did his research, won the right to manufacture the drug. Overcoming technical problems, Lilly perfected methods of large-scale collection of raw material extraction, purification, and mass production. Introduced insulin commercially in 1923 and, within a few years, enough insulin was being produced to meet the needs of diabetes patients around the world.
Vaccines began to be commercially produced in World War I, and, together with rising living standards, helped curb some infectious diseases. But the major onslaught against infection began in the late 1920s, when the German chemical giant I.G. Farben hired a young scientist named Gerhard Domagk. In 1933, experimenting with dyes, Domagk found that an orange-red dye called Prontosil killed bacteria in mice. A few weeks later, the substance saved the life of a baby dying of a blood stream staph infection. Called "sulfur drugs" after the active ingredient in the dye, these medicines were found to halt the growth and proliferation of bacteria while the body's natural defense fought off the infection.
The Magic Mold
Penicillin, the great break through against infection of the 20th century, had actually been discovered - but not developed - in 1928. Returning from vacation, Dr. Alexander Fleming, a bacteriologist at London's St. Mary's Hospital, found that a mysterious mold has sprouted in a petri dish. Bacteria covered the entire dish - except where the mold was. Fleming noted the mold's anti-bacterial action and named it penicillin, but failed to develop it. In 1940, Oxford University scientists Howard Florey and Ernest Chain developed penicillin into a therapeutic agent, but in 1941, could not produce enough of the compound to cure a policeman with severe septicemia. The patient improved when the drug was administered, but died when the meager supply was exhausted. By 1943, several U.S. based pharmaceutical companies were mass-producing purified penicillin. By 1944, sufficient penicillin was available to treat all severe battle wounds suffered by U.S. troops in the D-Day battles. In the 1950s, known as the decade of antibiotics, new breakthroughs - to treat tuberculosis and other infections - followed swiftly.
Progress Against Cancer
Cancer has been known and studied since antiquity, but in the words of one scholar: " Before the twentieth century, the main institutions dealing with cancer were hospitals to die in."
Early hopes for treating cancer focused on the mustard gas used in the First World War, the first chemotherapy agent for cancer. Unfortunately, the gas killed healthy cells as well as cancer cells and at best delayed death for a short time. Similarly, children with leukemia were treated with cortisone drugs which prolonged remissions for only a short time. In 1948 Lederic Laboratories developed methotrexate one of the earliest anticancer agents and an anti-metabolite that destroys cancer cells. George Hitchings and Gertrude Elion developed anti-metabolites for scule leukemia in the late 1940s and early 1950s, while working at the Burroughs Wellcome Co.
This and other early work formed the basis for the remarkable progress made against cancer in recent decades. According to the National Cancer Institute for, deaths from all cancers combined (as well as for the top 10 cancer sites) declined in the United States between 1990 and 1997, and eight out of ten children now survive leukemia. Said John R. Selfrin, Ph.D., CFO of the American Cancer Society: "Cancer death rates have been falling since 1991, and since 1995 that decline has been even more rapid. This gives us great hope that in the new millennium, our dreams of conquering cancer are closer than ever to becoming a reality."
A March 2001 survey by the Pharmaceutical Research and Manufactures of America PhRMA) found 402 new medicines in development for cancer.
The #1 Killer - Heart Disease
Heart disease has topped the list of killer diseases of Americans for decades, but thanks in large part to new medicines, deaths from heart disease have been cut by more than half since 1950.
The first known heart medicine was discovered in an English garden in 1799, when physician John Ferriar noted the effect of dried leaves of the common foxglove plant, Digitalis Purpuro on heart action. Still used in heart medications, digitalis slows the force of the heart contractions and increases the amount of blood pumped per heartbeat. In 1867, nitroglycerin, a key ingredient of dynamite, joined the armamentarium against heart disease, to relieve angina. In 1901, drug company and university scientists isolated adrenaline from the glands of cattle and used it in medicines to stimulate the heart.
Until relatively recently, however, there were few medicines to treat some of the underlying causes of heart disease, such as high blood pressure and high cholesterol. When President Franklin D. Roosevelt developed high blood pressure in the early 1940s, all his doctors prescribed were sedatives and a low-salt diet. In 1949 Indian physician Roston Jal Vakil wrote a British medical journal about using the powdered root of the tropical plant Rauwolfia sepentina to lower blood. Three years later, drug company chemists isolated the active ingredient of the plant and made the drug resezione for high blood pressure.
The first diuretic to treat high blood pressure was approved in 1950. The first clinically used beta-blocker appeared in 1967. The first ACE inhibitor and the first calcium channel blocker were approved in 1981.
In the early 1970s, drug company scientists looking for a drug for a poultry disease discovered an organism that inhibits an enzyme required for the synthesis of one of the building blocks of cholesterol. This serendipitous discovery led to a new class of drugs called sratins, which can cut the risk of coronary death by more than 40 percent. Clot-dissolving drugs, pioneered in the 1980s, can actually stop heart attacks in mid-stream before permanent damage to the heart is done.
Despite the progress, nearly 61 million Americans - more than one in five - suffer from at least one type of cardiovascular disease, and nearly a million Americans a year die of these diseases - more than 2,600 every day. Pharmaceutical companies are currently developing 122 new medicines for cardiovascular diseases, many of which use 21st century technologies.
The American Heart Association projects that if all major forms of heart and blood vessel disease were eliminated, U.S. life expectancy would rise by almost seen years and the economic savings would total more than $300 billion a year. Cardiovascular disease claimed about 950,000 lives in the U.S. in 1998, which is 40.6 percent of all deaths.
Conclusion
In the past 100 years, pharmaceutical research has helped transform health care from a largely palliative practice to a science-based endeavor. Due in part to this transformation and in part to improvements in sanitation, average life expectancy in the U.S. has increased from 47 years in 1900 to more that 76.5 years today.
In addition to longer lives, pharmaceutical progress has brought better lives to millions of people. It has consigned many infectious scourges of the past to history books; it has transformed mental illness from a misunderstood cause of shame and fear into a highly treatable condition. It has helped make old age a time of active independence, rather than disability, for many. It has made impressive inroads against cancer, heat disease, stroke, and many other diseases.
As the 21st century begins, pharmaceutical companies are continuing the battle against humankind's ancient enemies and meeting new challenges, including seeking better treatments and cures for AIDS and Alzheimer's disease.
