The History of Medicine
Robert Conrad Brunham, OBC, MD, FRCPC, FRSC
Professor Emeritus, Department of Medicine, University of British Columbia
Robert Conrad Brunham, OBC, MD, FRCPC, FRSC
Professor Emeritus, Department of Medicine, University of British Columbia
Introduction
The development of civilization catalyzed the development of three great systems of medicine. These are Traditional Chinese medicine, Traditional Indian Medicine (Ayurveda) and Western Medicine. All three systems have observation and theory-building as key components. Beginning during the European Renaissance, Western Medicine diverged from the other systems by adopting experimentation rather than authority as the method to resolve differences. Experimentation allowed Western Medicine to grow and it is now the major system of medicine throughout the world. Accordingly, in this essay Western Medicine is called modern medicine.
Modern medicine is the focus of this historical review. Modern medicine focusses on the diagnosis and treatment of disease using scientific evidence as the basis for treatment decisions. Modern medicine is based on an understanding of human biology and its evolutionary origin. The philosophical and ethical basis for modern medicine is based on humanism and naturalism.
This essay will review the history of key developments in modern medicine. It will focus on the development of drug therapeutics rather than surgery. Surgery, which is also based on science, also has a major role in disease treatment but has its own distinctive history.
This essay will review 28 key steps in the development of modern medicine based on narratives about the individual who brought about the change. The history will be reconstructed from the present back into the past and, therefore, only changes that have produced enduring impact will be emphasized. While the correct history of modern medicine, like other areas of social development, is characterized by many failures and blind alleys, this essay emphasizes only those changes that endured. The essay will summarize the key feature of the historical development of modern medicine and point out the impact of modern medicine on human life. The future of medicine will be imagined.
Innovations and Innovators in the Development of Modern Medicine
Twenty-eight steps and 51 individuals have shaped the development of modern medicine over the last 2500 years. Modern medicine had its philosophical and ethical origin in Greece and its scientific origin in Western Europe and North America. Islamic culture is the conduit by which Greek medicine arrived into the European Renaissance.
Hippocrates of Kos (460-370 BC)
Hippocrates was a unique individual, a lone original thinker in a demon-haunted world. He lived during the age of Greek rationality, as articulated by Socrates, Plato and Aristotle. He proposed that human disease has natural origins that are influenced by a person’s inherited constitution and their environment. He observed that disease appears in different persons with similar physical signs and courses of events. He observed outbreaks of the same disease occurring in different persons at the same time of the year and in specific geographic locations. He observed that most diseases spontaneously heal. Because of this tendency toward healing, he concluded that the first duty of a physician was to do no harm, primum non nocere. So timeless are Hippocrates’ writings that they are still read by today’s physicians. Hippocrates set modern medicine on the course that it’s on today.
Andreas Vesalius (1514-1564 AD)
It was nearly two millennia before the next person appeared who was to shape modern medicine. He was born in Belgium as Andries van Wezel, which he latinized as Andreas Vesalius. In 1543, the same year as Copernicus published his book On the Revolutions of the Celestial Spheres, Vesalius published his book On the Fabric of the Human Body. This was the first book to be published on human anatomy that was based on experimental observation of the dissection of the human cadaver. Just as Copenicus’ book triggered a Copernican revolution in astronomy, Versalius’ book triggered a similar revolution in medicine. For the first time, it was possible to consider the anatomical basis for health and disease. To this day, anatomy remains a fundamental science in modern medical education.
William Harvey (1578-1657 AD)
William Harvey was a graduate in 1602 of the same medical school, University of Padua, where Andreas Vesalius conducted his anatomical research. Harvey carried forward an inquisitive spirit into medicine. In 1628 he published his book entitled De Motu Cordis. In the book he reported evidence for the circulation of the blood powered by the heart as a pump and demonstrated the presence of venous valves to infer the circulation of blood from the arterial to the venous system. He conceptualized the body as composed of many mechanisms, of which circulation was one, a concept that continues to underpin modern medical research.
Giovanni Battista Morgagni (1682-1771 AD)
Giovanni Morgagni also conducted and taught anatomical studies at the University of Padua. He conducted his anatomical studies among individuals who died of disease. He was able to correlate specific diseases in life with anatomical sites of pathology at autopsy. This was the first step of reductionism in medicine, a trend in medical research that has continued to this day, down to the level of the cell and molecules. His book On the Seats and Causes of Disease was published in 1761. Even now anatomical pathology remains a key science in modern medicine.
Edward Jenner (1749-1823 AD)
Edward Jenner has probably saved more lives than any other physician in history. Since Greek times it had been observed that if an individual recovers from an infectious disease, they remain resistant to reinfection for the rest of their life. Edward Jenner developed a vaccine to prevent smallpox, which was eliminated from humanity in 1980. He noted that milkmaids who acquired cowpox from cattle were immune to smallpox. Cowpox was a much milder infection than smallpox. At this time in England, it was common practice to use material from smallpox lesions to cutaneously inoculate children to prevent smallpox. A mild case of smallpox was produced that protected against more severe disease in later life. Edward Jenner showed that cowpox inoculation was even safer to use than smallpox inoculation. His report entitled Inquiry into the Variolae Vaccine Known as Cowpox is an amazing story of scientific enlightenment.
Friedich Wilhelm Adam Serturner (1783-1841 AD)
Pierre-Joseph Pelletier (1788-1842 AD)
Joseph Caventou (1795-1877 AD)
At the start of the 19th century chemists made transformative changes in medicine. They extracted the active ingredients, such as morphine, quinine and colchicine, from medicinal plants. Theophrastus (371-287 BC) lived in the generation after Hippocrates and listed hundreds of plants that folk wisdom considered probably helpful in treating human disease. When these French chemists purified the biologically active substances from medicinal plants, it became possible to prove treatment efficacy and investigate their mode of action. Presently, over 6500 drugs have been identified that are useful in medicine, the majority of which are derived from eukaryotic and prokaryotic life forms. There exists a remarkable uniformity to the chemistry of all life forms.
Rene Laennec (1781-1826 AD)
Rene Laennec systematically investigated human disease by correlating the physical findings of disease observed in the living patient in a hospital bed with findings found at autopsy. He was especially interested in lung diseases such as tuberculosis, which was a common cause of death in Paris during his lifetime. He invented the stethoscope to detect lung abnormalities in tuberculosis during life. Tragically, he died at 45 years of age from tuberculosis, which he may have acquired during autopsy studies of patients who died of the disease. His approach to clinical pathological investigation remains a part of today’s medicine. The stethoscope remains the iconic diagnostic symbol of the bedside physician.
Claude Bernard (1813-1878 AD)
Claude Bernard created the medical science of physiology. He discovered the key biological principle of homeostasis, the notion that living organisms exist in a dynamic state far from equilibrium that depends on interactions among organ systems and circulating mediators. He identified the role of the pancreas in food digestion and the role of the liver in carbohydrate metabolism. He also discovered the autonomic nervous system and revolutionized medicine by conceiving of the method of experimental medicine, which is the laboratory basis for modern medical research today.
Rudolf Virchow (1821-1902 AD)
Rudolf Virchow identified the cellular basis for human anatomy and pathology. The cell concept of how life was structurally organized had just been recognized in biology and Virchow brought these ideas into medicine. In particular, he identified the cellular basis for inflammation and cancer. His textbook Cellular Pathology is still read today.
John Snow (1813-1858 AD)
John Snow introduced epidemiology into medicine. Before microbes were identified as causes of human disease, he mapped the distribution of cholera deaths in London’s Soho district and identified a single water pump station as the likely source. He speculated that contaminated water and not putrefied air (miasma) was the cause of the outbreak. As dramatic proof of the role of water as the cause of the cholera outbreak, he removed the pump handle and the cholera epidemic abruptly ended. John Snow created the modern medical discipline of public health.
Felix Hoppe-Seyler (1825-1895 AD)
Fredrick Meischner (1844-1895 AD)
When cells were recognized as the fundamental structural unit of the human body, their internal contents were unclear. These two medical scientists discovered that the main constituents of cells were two large molecular substances. Felix Hoppe-Seyler discovered the hemoglobin protein in red blood cells and his student, Fredrick Meischner, discovered nucleic acids, DNA and RNA, in white blood cells. This was of fundamental importance because many diseases were later traced to abnormalities in proteins or nucleic acids and many efficacious drugs in medicine were later identified as targeting the implicated protein.
Ignaz Semmelweiss (1818-1865 AD)
Louis Pasteur (1822-1895 AD)
Robert Koch (1843-1910 AD)
These three physician scientists arguably produced the greatest advance in modern medicine. They established the microbial causes of many human diseases and infectious disease became the paradigm for how major causes of disease could be understood and controlled. Ignaz Semmelweiss discovered the role of physicians in transmitting infection within the hospital setting and introduced hand washing as the key strategy to prevent nosocomial transmission, a strategy that remains in place today. Pasteur discovered microbial causes of several diseases and, building on the concept of Edward Jenner, introduced vaccination to prevent the morbidity of infections such as rabies. Robert Koch established the scientific principles by which microbial causes of infectious diseases are proven and discovered the microbe that causes tuberculosis.
Wilhelm Rontgen (1845-1923 AD)
Wilhelm Rontgen discovered the usefulness of electromagnetic x-rays in diagnostic imaging. He founded the field of diagnostic radiology, which has grown to include a wide spectrum of electromagnetic waves, radioisotope emission particles, ultrasound waves and magnetic/radio waves, to map the underlying structure of the human body. His discovery of x-rays involved imaging the skeletal structure of his wife’s hand, to which she excitedly explained, “I have now seen my death”. Diagnostic imaging has transformed the physician’s ability to recognize the anatomical signatures of disease in the human body during life.
Elie Metchnikoff (1845-1916 AD)
Paul Erlich (1854-1915 AD)
These two scientists discovered the cellular and molecular mediators of the immune system. Elie Metchnikoff discovered macrophages and Paul Erlich discovered antibody molecules. The immune system fascinates physicians because much like the nervous system it is capable of learning and memory. The immune system defends against infectious diseases and cancer. When dysregulated the immune system can attack harmless substances to cause allergy or autoimmune disease. Vaccination depends on the immune system’s key property of memory and is one of public health’s greatest tools.
Archibald Garrod (1857-1936 AD)
Archibald Garrod introduced Mendelian genetics into medicine by studying inborn errors of metabolism. He discovered alkaptonuria, a distinctive if not life-threatening disease that causes dark discolouration of urine when exposed to air. He noted the disease runs in families based on Mendelian principles and is commonly associated with first cousin marriages. Archibald Garrod realized that alkaptonuria is but one example of a whole range of poorly understood inherited diseases, such as albinism, cystinuria and pentosuria. In the latter part of the 20th century genetics has become a foundational aspect for the understanding of most diseases.
Fredrick Banting (1891-1941 AD)
Fredrick Banting discovered insulin in January 1922. In an exemplary case of bench to bedside research, he demonstrated that insulin treated the life-threatening metabolic abnormalities of type 1 diabetes mellitus in patients. Theodore Ryder was 6 years old when he was first treated with insulin in 1922. He lived until 1993, when he died at the age of 77, a medical miracle by any standard. Insulin is a therapeutic protein and was the first in the class of protein drugs. When the techniques of molecular biology and monoclonal antibody were developed a half century later, proteins became the commonest type of new therapeutic in medicine.
Alexander Flemming (1881-1955 AD)
Gerhard Domagk (1895-1964 AD)
Alexander Flemming discovered penicillin naturally produced by the fungus Penicillium rubens. Gerhard Domagk discovered the antibacterial activity of a chemically synthesized azo dye attached to a sulphonamide group. These discoveries launched the antimicrobial era and dramatically reduced the impact of infectious diseases on human health. Antimicrobials enabled much of modern medicine, including surgery, intensive care, cancer chemotherapy and organ transplantation. Much of modern medicine carried out in hospitals absolutely depends on antimicrobials. The rise of antimicrobial drug resistance threatens many of these advances and contending with drug resistance remains a core challenge for medical research today.
Otto Warburg (1883-1970 AD)
Hans Krebs (1900-1981 AD)
Peter Mitchell (1920-1992 AD)
Fritz Lippmann (1899-1986 AD)
These individuals mapped out the energy generating biochemical pathways that power metabolism, synthesis, movement and replication of the cell. Elucidating energy generating mechanisms has been key to understanding normal physiology and aging. Understanding energy generating pathways in the cell has shed light on the origin of cellular life on Earth.
Oswald Avery (1877-1955 AD)
Oswald Avery conducted decades of research on the mechanisms by which the pneumococcus bacterium produced pneumonia. Such studies identified the essential role of the bacterial capsule in disease pathogenesis. Oswald Avery demonstrated that strains of pneumococcus acquired different types of capsule when DNA but not protein was used to transform the microbial cell, thereby proving that the molecular basis for the gene was DNA. This transformed understanding of genetics and the molecular biology of the cell.
JBS Haldane (1892-1964 AD)
Anthony Allison (1897-2014 AD)
These scientists demonstrated for the first time the importance of evolution to human disease. JBS Haldane theorized that the sickle cell mutation in hemoglobin provided protection to erythrocyte replication of the Plasmodium parasite. Anthony Allison showed that geographic distribution of malaria exactly mapped the distribution of sickle cell disease in human populations in Africa. These investigators demonstrated the selective effects of malaria on the distribution of specific mutations in the human genome. This example has become the first of many illustrating the selective impact of pathogens on the evolution of mutations in the human genome.
Ronald Fisher (1890-1962 AD)
Austin Bradford Hill (1897-1991 AD)
These investigators developed the mathematical tools to conduct randomized clinical trials in medicine. Randomized clinical trials overcome the inherent biases in observational epidemiology and drug studies of therapeutic efficacy. Randomized clinical trials are one of the few ways to prove causality in medicine. The first use of a randomized clinical trial demonstrated the effectiveness of streptomycin in treating tuberculosis. Randomized clinical trials provide the foundation for evidence-based medicine, which now characterizes modern medicine.
Linus Pauling (1901-1994 AD)
Francis Crick (1916-2004 AD)
Rosalind Franklin (1920-1958 AD)
James Watson (1928- )
These four scientists developed concepts regarding the molecular biology of the cell, which underpins almost all fundamental medical research today. Linus Pauling elucidated the relationship between protein structure and function with a focus on hemoglobin. James Watson and Francis Crick proposed a model of DNA structure based on the experimental data of Rosalind Franklin. Francis Crick conceptualized the central dogma of the cell based on the flow of information from DNA to RNA to protein.
Gertrude Elion (1918-1999 AD)
George Hitching (1905-1998 AD)
These scientists took advantage of improved understanding of the molecular biology of the cell to rationally design new drugs. They used understanding of the protein target to design new small molecule drugs to alter the function of the protein target. Through this method, new drugs were developed to treat microbial infection, viral pathogens, cancer cells and enable organ transplantation. Rational drug design underpins much of small molecule drug design today.
Cesar Milstein (1927-2002 AD)
Georges Kohler (1946-1995 AD)
These scientists developed the technology to produce monoclonal antibodies in perpetuity. These antibodies can in turn be engineered to improve or alter their specificity. Monoclonal antibodies have dramatically expanded treatments for autoimmune diseases and cancers. Most new drugs are proteins now based on the monoclonal antibody platform.
Joseph Goldstein (1940- )
Michael Brown ( 1941- )
Atheroscleorotic cardiovascular disease is the most common cause of age-related death. Elevated levels of cholesterol are the most important proximate cause of atherosclerosis. These investigators defined the role of the low-density lipoprotein metabolic pathway through which cholesterol produces atherosclerosis and developed drugs that safely inhibit liver synthesis of low-density lipoprotein cholesterol. These drugs have markedly improved the treatment and prevention of atherosclerosis. They are one of medicine’s greatest benefits to humanity.
Harold Varmus (1939- )
J Michael Bishop (1936- )
Cancer is the second leading cause of age-related death. These scientists discovered several of the many mutated genes that cause cancer. The proteins produced by mutated genes are now the targets for rationally designed drugs or monoclonal antibodies. These drugs have substantially advanced cancer cure rates. Cancer, like atherosclerosis, is now coming under medical control.
Craig Venter (1946- )
Svante Paabo (1955- )
These investigators introduced genomics into medicine. Genomics involves the determination of the entire DNA sequence of an organism from viruses to humans. Genomics has uncovered the role of evolution in medicine, including the role of specific gene variation in disease etiology. Genomics is the main method for elucidating the role of genes in disease through genome-wide association studies. Genomics has determined the natural origin of many emerging infectious diseases. Genomics is an essential tool for public health to map the origins and spread of emerging microbes during epidemics and pandemics, as was so vividly seen during COVID-19.
Jennifer Doudna (1964- )
Emmanuelle Charpentier (1968- )
Katalin Kariko (1955- )
Drew Weissman (1959- )
These investigators have exploited the improved molecular understanding of the cell to develop new nucleic acid targeted therapies. Jennifer Doudna and Emmanuelle Charpentier developed the gene editing technique called CRISPR to treat genetic diseases such as sickle cell anemia and thalassemia. Katalin Kariko and Drew Weissman developed new methods to deliver therapeutic RNA into cells. They invented the method for RNA vaccinology that proved essential in halting the COVID-19 pandemic. It is likely that future medical therapeutics and vaccines will be based on CRISPR and RNA molecules.
Interpretation of the History of Modern Medicine
Modern medicine is a remarkably young science, a product of innovations accruing during the last two centuries. Its origin in Greece over 2500 years ago shows how individuals such as Hippocrates, Vesalius, Harvey and Morgagni worked to create the foundations of modern medicine. It is remarkable how the University of Padua began to nucleate a centre of inquiry into the foundations of medicine and then how, during the 19th and 20th centuries, teams of individuals worked to create modern medicine. Early achievements in medicine had more to do with improved understanding of the processes that produce disease and only later were methods found to alter those processes and treat disease. Surprisingly, it was only 70 years ago that randomized clinical trial methods were developed that allowed for treatments to be proven effective at treating disease. Before that time, Hippocrates dictum primum non nocere should have reigned supreme but few physicians were able to restrain themselves from harmful interventions that characterized so much of medical history before the modern era.
Overall, the history of medicine is characterized by the contributions of individual geniuses in its early history and by the contributions of groups of interacting individuals in its later history. The exponentially expanding human population since the onset of the industrial revolution may have created the emergence of the collective mind necessary for these advancements in modern medicine.
Out of the 51 individuals who are identified as key innovators of modern medicine, only five are women. This illustrates the major historical barriers that existed for women in medicine as well as other areas of life. More women are featured as innovators in modern medicine in recent times, hopefully indicating a reduction in those barriers.
The Impact and Future of Modern Medicine
During the 20th century, in parallel with advancements in modern medicine, human life expectancy more than doubled. This occurred globally, although it began first in Europe and the Americas tracking the origin and spread of modern medicine. Of great importance, the extension of human life has not been accompanied by expansion of lifespan. Human lifespan appears fixed at approximately 115 years and the proportion of persons living to advanced age has expanded under the influence of modern medicine. Death among aging adults is commonly due to cardiovascular disease (atherosclerosis), central nervous system disease, cancer or complications of diabetes mellitus. Death among supercenturians (110 years of age or greater) is not accompanied by these diseases. Rather, death in these individuals appears to be due to loss of organ reserve and absence of homeostasis after a brief three or more months of illness. Thus the goal of modern medicine is to eliminate those age-related diseases that contribute to premature mortality and compress morbidity to a small time interval near the end of a natural lifespan of between 110 and 115 years of life. This goal appears achievable but will require additional innovations in modern medicine and public health.
The development of civilization catalyzed the development of three great systems of medicine. These are Traditional Chinese medicine, Traditional Indian Medicine (Ayurveda) and Western Medicine. All three systems have observation and theory-building as key components. Beginning during the European Renaissance, Western Medicine diverged from the other systems by adopting experimentation rather than authority as the method to resolve differences. Experimentation allowed Western Medicine to grow and it is now the major system of medicine throughout the world. Accordingly, in this essay Western Medicine is called modern medicine.
Modern medicine is the focus of this historical review. Modern medicine focusses on the diagnosis and treatment of disease using scientific evidence as the basis for treatment decisions. Modern medicine is based on an understanding of human biology and its evolutionary origin. The philosophical and ethical basis for modern medicine is based on humanism and naturalism.
This essay will review the history of key developments in modern medicine. It will focus on the development of drug therapeutics rather than surgery. Surgery, which is also based on science, also has a major role in disease treatment but has its own distinctive history.
This essay will review 28 key steps in the development of modern medicine based on narratives about the individual who brought about the change. The history will be reconstructed from the present back into the past and, therefore, only changes that have produced enduring impact will be emphasized. While the correct history of modern medicine, like other areas of social development, is characterized by many failures and blind alleys, this essay emphasizes only those changes that endured. The essay will summarize the key feature of the historical development of modern medicine and point out the impact of modern medicine on human life. The future of medicine will be imagined.
Innovations and Innovators in the Development of Modern Medicine
Twenty-eight steps and 51 individuals have shaped the development of modern medicine over the last 2500 years. Modern medicine had its philosophical and ethical origin in Greece and its scientific origin in Western Europe and North America. Islamic culture is the conduit by which Greek medicine arrived into the European Renaissance.
Hippocrates of Kos (460-370 BC)
Hippocrates was a unique individual, a lone original thinker in a demon-haunted world. He lived during the age of Greek rationality, as articulated by Socrates, Plato and Aristotle. He proposed that human disease has natural origins that are influenced by a person’s inherited constitution and their environment. He observed that disease appears in different persons with similar physical signs and courses of events. He observed outbreaks of the same disease occurring in different persons at the same time of the year and in specific geographic locations. He observed that most diseases spontaneously heal. Because of this tendency toward healing, he concluded that the first duty of a physician was to do no harm, primum non nocere. So timeless are Hippocrates’ writings that they are still read by today’s physicians. Hippocrates set modern medicine on the course that it’s on today.
Andreas Vesalius (1514-1564 AD)
It was nearly two millennia before the next person appeared who was to shape modern medicine. He was born in Belgium as Andries van Wezel, which he latinized as Andreas Vesalius. In 1543, the same year as Copernicus published his book On the Revolutions of the Celestial Spheres, Vesalius published his book On the Fabric of the Human Body. This was the first book to be published on human anatomy that was based on experimental observation of the dissection of the human cadaver. Just as Copenicus’ book triggered a Copernican revolution in astronomy, Versalius’ book triggered a similar revolution in medicine. For the first time, it was possible to consider the anatomical basis for health and disease. To this day, anatomy remains a fundamental science in modern medical education.
William Harvey (1578-1657 AD)
William Harvey was a graduate in 1602 of the same medical school, University of Padua, where Andreas Vesalius conducted his anatomical research. Harvey carried forward an inquisitive spirit into medicine. In 1628 he published his book entitled De Motu Cordis. In the book he reported evidence for the circulation of the blood powered by the heart as a pump and demonstrated the presence of venous valves to infer the circulation of blood from the arterial to the venous system. He conceptualized the body as composed of many mechanisms, of which circulation was one, a concept that continues to underpin modern medical research.
Giovanni Battista Morgagni (1682-1771 AD)
Giovanni Morgagni also conducted and taught anatomical studies at the University of Padua. He conducted his anatomical studies among individuals who died of disease. He was able to correlate specific diseases in life with anatomical sites of pathology at autopsy. This was the first step of reductionism in medicine, a trend in medical research that has continued to this day, down to the level of the cell and molecules. His book On the Seats and Causes of Disease was published in 1761. Even now anatomical pathology remains a key science in modern medicine.
Edward Jenner (1749-1823 AD)
Edward Jenner has probably saved more lives than any other physician in history. Since Greek times it had been observed that if an individual recovers from an infectious disease, they remain resistant to reinfection for the rest of their life. Edward Jenner developed a vaccine to prevent smallpox, which was eliminated from humanity in 1980. He noted that milkmaids who acquired cowpox from cattle were immune to smallpox. Cowpox was a much milder infection than smallpox. At this time in England, it was common practice to use material from smallpox lesions to cutaneously inoculate children to prevent smallpox. A mild case of smallpox was produced that protected against more severe disease in later life. Edward Jenner showed that cowpox inoculation was even safer to use than smallpox inoculation. His report entitled Inquiry into the Variolae Vaccine Known as Cowpox is an amazing story of scientific enlightenment.
Friedich Wilhelm Adam Serturner (1783-1841 AD)
Pierre-Joseph Pelletier (1788-1842 AD)
Joseph Caventou (1795-1877 AD)
At the start of the 19th century chemists made transformative changes in medicine. They extracted the active ingredients, such as morphine, quinine and colchicine, from medicinal plants. Theophrastus (371-287 BC) lived in the generation after Hippocrates and listed hundreds of plants that folk wisdom considered probably helpful in treating human disease. When these French chemists purified the biologically active substances from medicinal plants, it became possible to prove treatment efficacy and investigate their mode of action. Presently, over 6500 drugs have been identified that are useful in medicine, the majority of which are derived from eukaryotic and prokaryotic life forms. There exists a remarkable uniformity to the chemistry of all life forms.
Rene Laennec (1781-1826 AD)
Rene Laennec systematically investigated human disease by correlating the physical findings of disease observed in the living patient in a hospital bed with findings found at autopsy. He was especially interested in lung diseases such as tuberculosis, which was a common cause of death in Paris during his lifetime. He invented the stethoscope to detect lung abnormalities in tuberculosis during life. Tragically, he died at 45 years of age from tuberculosis, which he may have acquired during autopsy studies of patients who died of the disease. His approach to clinical pathological investigation remains a part of today’s medicine. The stethoscope remains the iconic diagnostic symbol of the bedside physician.
Claude Bernard (1813-1878 AD)
Claude Bernard created the medical science of physiology. He discovered the key biological principle of homeostasis, the notion that living organisms exist in a dynamic state far from equilibrium that depends on interactions among organ systems and circulating mediators. He identified the role of the pancreas in food digestion and the role of the liver in carbohydrate metabolism. He also discovered the autonomic nervous system and revolutionized medicine by conceiving of the method of experimental medicine, which is the laboratory basis for modern medical research today.
Rudolf Virchow (1821-1902 AD)
Rudolf Virchow identified the cellular basis for human anatomy and pathology. The cell concept of how life was structurally organized had just been recognized in biology and Virchow brought these ideas into medicine. In particular, he identified the cellular basis for inflammation and cancer. His textbook Cellular Pathology is still read today.
John Snow (1813-1858 AD)
John Snow introduced epidemiology into medicine. Before microbes were identified as causes of human disease, he mapped the distribution of cholera deaths in London’s Soho district and identified a single water pump station as the likely source. He speculated that contaminated water and not putrefied air (miasma) was the cause of the outbreak. As dramatic proof of the role of water as the cause of the cholera outbreak, he removed the pump handle and the cholera epidemic abruptly ended. John Snow created the modern medical discipline of public health.
Felix Hoppe-Seyler (1825-1895 AD)
Fredrick Meischner (1844-1895 AD)
When cells were recognized as the fundamental structural unit of the human body, their internal contents were unclear. These two medical scientists discovered that the main constituents of cells were two large molecular substances. Felix Hoppe-Seyler discovered the hemoglobin protein in red blood cells and his student, Fredrick Meischner, discovered nucleic acids, DNA and RNA, in white blood cells. This was of fundamental importance because many diseases were later traced to abnormalities in proteins or nucleic acids and many efficacious drugs in medicine were later identified as targeting the implicated protein.
Ignaz Semmelweiss (1818-1865 AD)
Louis Pasteur (1822-1895 AD)
Robert Koch (1843-1910 AD)
These three physician scientists arguably produced the greatest advance in modern medicine. They established the microbial causes of many human diseases and infectious disease became the paradigm for how major causes of disease could be understood and controlled. Ignaz Semmelweiss discovered the role of physicians in transmitting infection within the hospital setting and introduced hand washing as the key strategy to prevent nosocomial transmission, a strategy that remains in place today. Pasteur discovered microbial causes of several diseases and, building on the concept of Edward Jenner, introduced vaccination to prevent the morbidity of infections such as rabies. Robert Koch established the scientific principles by which microbial causes of infectious diseases are proven and discovered the microbe that causes tuberculosis.
Wilhelm Rontgen (1845-1923 AD)
Wilhelm Rontgen discovered the usefulness of electromagnetic x-rays in diagnostic imaging. He founded the field of diagnostic radiology, which has grown to include a wide spectrum of electromagnetic waves, radioisotope emission particles, ultrasound waves and magnetic/radio waves, to map the underlying structure of the human body. His discovery of x-rays involved imaging the skeletal structure of his wife’s hand, to which she excitedly explained, “I have now seen my death”. Diagnostic imaging has transformed the physician’s ability to recognize the anatomical signatures of disease in the human body during life.
Elie Metchnikoff (1845-1916 AD)
Paul Erlich (1854-1915 AD)
These two scientists discovered the cellular and molecular mediators of the immune system. Elie Metchnikoff discovered macrophages and Paul Erlich discovered antibody molecules. The immune system fascinates physicians because much like the nervous system it is capable of learning and memory. The immune system defends against infectious diseases and cancer. When dysregulated the immune system can attack harmless substances to cause allergy or autoimmune disease. Vaccination depends on the immune system’s key property of memory and is one of public health’s greatest tools.
Archibald Garrod (1857-1936 AD)
Archibald Garrod introduced Mendelian genetics into medicine by studying inborn errors of metabolism. He discovered alkaptonuria, a distinctive if not life-threatening disease that causes dark discolouration of urine when exposed to air. He noted the disease runs in families based on Mendelian principles and is commonly associated with first cousin marriages. Archibald Garrod realized that alkaptonuria is but one example of a whole range of poorly understood inherited diseases, such as albinism, cystinuria and pentosuria. In the latter part of the 20th century genetics has become a foundational aspect for the understanding of most diseases.
Fredrick Banting (1891-1941 AD)
Fredrick Banting discovered insulin in January 1922. In an exemplary case of bench to bedside research, he demonstrated that insulin treated the life-threatening metabolic abnormalities of type 1 diabetes mellitus in patients. Theodore Ryder was 6 years old when he was first treated with insulin in 1922. He lived until 1993, when he died at the age of 77, a medical miracle by any standard. Insulin is a therapeutic protein and was the first in the class of protein drugs. When the techniques of molecular biology and monoclonal antibody were developed a half century later, proteins became the commonest type of new therapeutic in medicine.
Alexander Flemming (1881-1955 AD)
Gerhard Domagk (1895-1964 AD)
Alexander Flemming discovered penicillin naturally produced by the fungus Penicillium rubens. Gerhard Domagk discovered the antibacterial activity of a chemically synthesized azo dye attached to a sulphonamide group. These discoveries launched the antimicrobial era and dramatically reduced the impact of infectious diseases on human health. Antimicrobials enabled much of modern medicine, including surgery, intensive care, cancer chemotherapy and organ transplantation. Much of modern medicine carried out in hospitals absolutely depends on antimicrobials. The rise of antimicrobial drug resistance threatens many of these advances and contending with drug resistance remains a core challenge for medical research today.
Otto Warburg (1883-1970 AD)
Hans Krebs (1900-1981 AD)
Peter Mitchell (1920-1992 AD)
Fritz Lippmann (1899-1986 AD)
These individuals mapped out the energy generating biochemical pathways that power metabolism, synthesis, movement and replication of the cell. Elucidating energy generating mechanisms has been key to understanding normal physiology and aging. Understanding energy generating pathways in the cell has shed light on the origin of cellular life on Earth.
Oswald Avery (1877-1955 AD)
Oswald Avery conducted decades of research on the mechanisms by which the pneumococcus bacterium produced pneumonia. Such studies identified the essential role of the bacterial capsule in disease pathogenesis. Oswald Avery demonstrated that strains of pneumococcus acquired different types of capsule when DNA but not protein was used to transform the microbial cell, thereby proving that the molecular basis for the gene was DNA. This transformed understanding of genetics and the molecular biology of the cell.
JBS Haldane (1892-1964 AD)
Anthony Allison (1897-2014 AD)
These scientists demonstrated for the first time the importance of evolution to human disease. JBS Haldane theorized that the sickle cell mutation in hemoglobin provided protection to erythrocyte replication of the Plasmodium parasite. Anthony Allison showed that geographic distribution of malaria exactly mapped the distribution of sickle cell disease in human populations in Africa. These investigators demonstrated the selective effects of malaria on the distribution of specific mutations in the human genome. This example has become the first of many illustrating the selective impact of pathogens on the evolution of mutations in the human genome.
Ronald Fisher (1890-1962 AD)
Austin Bradford Hill (1897-1991 AD)
These investigators developed the mathematical tools to conduct randomized clinical trials in medicine. Randomized clinical trials overcome the inherent biases in observational epidemiology and drug studies of therapeutic efficacy. Randomized clinical trials are one of the few ways to prove causality in medicine. The first use of a randomized clinical trial demonstrated the effectiveness of streptomycin in treating tuberculosis. Randomized clinical trials provide the foundation for evidence-based medicine, which now characterizes modern medicine.
Linus Pauling (1901-1994 AD)
Francis Crick (1916-2004 AD)
Rosalind Franklin (1920-1958 AD)
James Watson (1928- )
These four scientists developed concepts regarding the molecular biology of the cell, which underpins almost all fundamental medical research today. Linus Pauling elucidated the relationship between protein structure and function with a focus on hemoglobin. James Watson and Francis Crick proposed a model of DNA structure based on the experimental data of Rosalind Franklin. Francis Crick conceptualized the central dogma of the cell based on the flow of information from DNA to RNA to protein.
Gertrude Elion (1918-1999 AD)
George Hitching (1905-1998 AD)
These scientists took advantage of improved understanding of the molecular biology of the cell to rationally design new drugs. They used understanding of the protein target to design new small molecule drugs to alter the function of the protein target. Through this method, new drugs were developed to treat microbial infection, viral pathogens, cancer cells and enable organ transplantation. Rational drug design underpins much of small molecule drug design today.
Cesar Milstein (1927-2002 AD)
Georges Kohler (1946-1995 AD)
These scientists developed the technology to produce monoclonal antibodies in perpetuity. These antibodies can in turn be engineered to improve or alter their specificity. Monoclonal antibodies have dramatically expanded treatments for autoimmune diseases and cancers. Most new drugs are proteins now based on the monoclonal antibody platform.
Joseph Goldstein (1940- )
Michael Brown ( 1941- )
Atheroscleorotic cardiovascular disease is the most common cause of age-related death. Elevated levels of cholesterol are the most important proximate cause of atherosclerosis. These investigators defined the role of the low-density lipoprotein metabolic pathway through which cholesterol produces atherosclerosis and developed drugs that safely inhibit liver synthesis of low-density lipoprotein cholesterol. These drugs have markedly improved the treatment and prevention of atherosclerosis. They are one of medicine’s greatest benefits to humanity.
Harold Varmus (1939- )
J Michael Bishop (1936- )
Cancer is the second leading cause of age-related death. These scientists discovered several of the many mutated genes that cause cancer. The proteins produced by mutated genes are now the targets for rationally designed drugs or monoclonal antibodies. These drugs have substantially advanced cancer cure rates. Cancer, like atherosclerosis, is now coming under medical control.
Craig Venter (1946- )
Svante Paabo (1955- )
These investigators introduced genomics into medicine. Genomics involves the determination of the entire DNA sequence of an organism from viruses to humans. Genomics has uncovered the role of evolution in medicine, including the role of specific gene variation in disease etiology. Genomics is the main method for elucidating the role of genes in disease through genome-wide association studies. Genomics has determined the natural origin of many emerging infectious diseases. Genomics is an essential tool for public health to map the origins and spread of emerging microbes during epidemics and pandemics, as was so vividly seen during COVID-19.
Jennifer Doudna (1964- )
Emmanuelle Charpentier (1968- )
Katalin Kariko (1955- )
Drew Weissman (1959- )
These investigators have exploited the improved molecular understanding of the cell to develop new nucleic acid targeted therapies. Jennifer Doudna and Emmanuelle Charpentier developed the gene editing technique called CRISPR to treat genetic diseases such as sickle cell anemia and thalassemia. Katalin Kariko and Drew Weissman developed new methods to deliver therapeutic RNA into cells. They invented the method for RNA vaccinology that proved essential in halting the COVID-19 pandemic. It is likely that future medical therapeutics and vaccines will be based on CRISPR and RNA molecules.
Interpretation of the History of Modern Medicine
Modern medicine is a remarkably young science, a product of innovations accruing during the last two centuries. Its origin in Greece over 2500 years ago shows how individuals such as Hippocrates, Vesalius, Harvey and Morgagni worked to create the foundations of modern medicine. It is remarkable how the University of Padua began to nucleate a centre of inquiry into the foundations of medicine and then how, during the 19th and 20th centuries, teams of individuals worked to create modern medicine. Early achievements in medicine had more to do with improved understanding of the processes that produce disease and only later were methods found to alter those processes and treat disease. Surprisingly, it was only 70 years ago that randomized clinical trial methods were developed that allowed for treatments to be proven effective at treating disease. Before that time, Hippocrates dictum primum non nocere should have reigned supreme but few physicians were able to restrain themselves from harmful interventions that characterized so much of medical history before the modern era.
Overall, the history of medicine is characterized by the contributions of individual geniuses in its early history and by the contributions of groups of interacting individuals in its later history. The exponentially expanding human population since the onset of the industrial revolution may have created the emergence of the collective mind necessary for these advancements in modern medicine.
Out of the 51 individuals who are identified as key innovators of modern medicine, only five are women. This illustrates the major historical barriers that existed for women in medicine as well as other areas of life. More women are featured as innovators in modern medicine in recent times, hopefully indicating a reduction in those barriers.
The Impact and Future of Modern Medicine
During the 20th century, in parallel with advancements in modern medicine, human life expectancy more than doubled. This occurred globally, although it began first in Europe and the Americas tracking the origin and spread of modern medicine. Of great importance, the extension of human life has not been accompanied by expansion of lifespan. Human lifespan appears fixed at approximately 115 years and the proportion of persons living to advanced age has expanded under the influence of modern medicine. Death among aging adults is commonly due to cardiovascular disease (atherosclerosis), central nervous system disease, cancer or complications of diabetes mellitus. Death among supercenturians (110 years of age or greater) is not accompanied by these diseases. Rather, death in these individuals appears to be due to loss of organ reserve and absence of homeostasis after a brief three or more months of illness. Thus the goal of modern medicine is to eliminate those age-related diseases that contribute to premature mortality and compress morbidity to a small time interval near the end of a natural lifespan of between 110 and 115 years of life. This goal appears achievable but will require additional innovations in modern medicine and public health.