A History of Medicine, part 5

25 November 2008


This is the fifth part of an extensive essay on the origins of modern medicine. The first four parts can be read at Brussels Journal, Atlas Shrugs, EuropeNews and Gates of Vienna.

Microscopes were allegedly invented by the Dutch spectacle maker Zacharias Jansen (ca. 1580 - ca. 1638) just before the year 1600 or by the Dutch lensmaker Hans Lippershey (1570–1619), who is often credited with having made the first practical telescope in 1608 (a design Galileo Galilei soon improved).

Other candidates have been suggested as possible inventors, too. What we can say with certainty is that the microscope had been introduced before 1610. Among the first persons to achieve good results from the new invention, with remarkable levels of magnifications for his time, was a seventeenth-century Dutchman called Antoni van Leeuwenhoek. Bill Bryson explains in his entertaining A Short History of Nearly Everything:

Though he had little formal education and no background in science, he was a perceptive and dedicated observer and a technical genius. To this day it is not known how he got such magnificent magnifications from such simple handheld devices….

Over a period of fifty years - beginning, remarkably enough, when he was already past forty – Leeuwenhoek made almost two hundred reports to the Royal Society, all written in Low Dutch, the only tongue of which he was master….

In 1683 Leeuwenhoek discovered bacteria – but that was about as far as progress could get in the next century and a half, because of the limitations of microscope technology.

Not until 1831 would anyone first see the nucleus of a cell – it was found by the Scottish botanist Robert Brown, that frequent but always shadowy visitor to the history of science. Brown, who lived from 1773 to 1858, called it nucleus from the Latin nucula, meaning little nut or kernel.

Only in 1839, however, did anyone realize that all living matter is cellular. It was Theodor Schwann, a German, who had this insight, and it was not only comparatively late, as scientific insights go, but not widely embraced at first.Robert Brown (1773-1858) spent years doing botanic research in Australia during the early 1800s. The so-called Brownian motion, the random movement of small particles in a liquid or gas, is named after him. Theodor Schwann (1810–1882) was the co-founder of the cell theory along with two other Germans, Matthias Jakob Schleiden (1804-1881) and Rudolf Virchow (1821–1902).

The invention of both the telescope and the microscope had been made during the first decade of the 1600s, and both instruments were the result of improvements in lens grinding among Dutch eyeglass makers. However, while the introduction of the telescope made big and lasting changes the very first time it was used for astronomical observation by Galileo Galilei, it took much longer for the microscope to achieve major scientific changes. Symptomatically, most people know that Galileo had great skills in making and using telescopes; far fewer know that he was equally skilled at making microscopes.

There was some good work done in microscopy already during the first century of the instrument's existence. The Italian physician Marcello Malpighi (1628-1694) did interesting studies related to medicine, and the English polymath Robert Hooke (1635–1703) published Micrographia, the first substantial book on microscopy by any scientist, in 1665. As John Gribbin says in The Scientists:

Hooke was not the first microscopist. Several people had followed up Galileo's lead by the 1660s and, as we have seen, Malpighi in particular had already made important discoveries, especially those concerning the circulation of the blood, with the new instrument. But Malpighi's observations had been reported piece by piece to the scientific community more or less as they had been made.

The same is largely true of Hooke's contemporary Antoni van Leeuwenhoek (1632-1723), a Dutch draper who had no formal academic training but made a series of astounding discoveries (mostly communicated through the Royal Society) using microscopes that he made himself. These instruments consisted of very small, convex lenses (some the size of pinheads) mounted in strips of metal and held close to the eye – they were really just incredibly powerful magnifying glasses, but some could magnify 200 or 300 times.

Van Leeuwenhoek's most important discovery was the existence of moving creatures (which he recognized as forms of life) in droplets of water – microorganisms including varieties now known as protozoa, rotifera and bacteria.In Gribbin's view, though Leuwenhoek's studies were significant and impressive considering the fact that he was an amateur, he was a one-off, using unconventional techniques and instruments. Hooke represented the mainstream path along which microscopy developed and packaged his discoveries in a single, accessible volume with scientifically accurate drawings.

Hooke described the structure of feathers, a butterfly's wing and identified fossils as remains of once-living creatures and plants, which was still far from self-evident in the seventeenth century. Nevertheless, microscopy didn't produce real changes in medicine until significantly improved instruments constructed on the basis of sound optical theory, essentially reaching the same level of quality as the light microscopes in use today, had been created after the mid-nineteenth century.

A leading force behind this was the brilliant German mathematician and physicist Ernst Abbe (1840–1905), in cooperation with Carl Zeiss (1816–1888). During this period the Germans played a leading role in laboratory medicine. Michael Kennedy explains:

In 1846, Carl Zeiss opened his workshop in Jena and German lenses quickly became the best in the world. Jacob Henle (1809-85) produced the first textbook of combined gross and microscopic anatomy in 1866 and encouraged the use of microscopes by students. The Royal College of Surgeons in England instituted courses in gross and microscopic anatomy in 1848.

German universities invested in academic science, with the support of rulers concerned about national prestige, and Germany quickly adopted research-based medical science, which would pay great dividends by the end of the century. Chemistry at last was to play the role once emphasized by Paracelsus four centuries earlier. The Germans began to study what we now call organic chemistry.As Joel Mokyr writes in The Gifts of Athena: Historical Origins of the Knowledge Economy:

The invention of the modern compound microscope by Joseph J. Lister (father of the famous surgeon) in 1830 serves as another good example. Lister was an amateur optician, whose revolutionary method of grinding lenses greatly improved image resolution by eliminating spherical aberrations.

His invention changed microscopy from an amusing diversion to a serious scientific endeavor and eventually allowed Pasteur, Koch, and their disciples to refute spontaneous generation and to establish the germ theory, a topic I return to below.

The germ theory was one of the most revolutionary changes in useful knowledge in human history and mapped into a large number of new techniques in medicine, both preventive and clinical. The speed and intensity of this interaction took place was still slow, but it was accelerating, and by the close of the eighteenth century it had become self-sustaining. The improvements were made based on a mathematical optimization for combining lenses to minimize spherical aberration and reduced average image distortion by a huge proportion, from 19 to 3 percent. In plain words, the average microscope was now much better and more accurate than it had been a few generations before.

Although Antoni van Leeuwenhoek had probably spotted bacteria in his unusually good microscope already in the seventeenth century, the concept that infectious diseases were caused by living organisms too small to be seen by the naked human eye met with stubborn resistance. Kennedy again:

Girolamo Fracastoro, in 1546, had proposed the cause of infectious diseases as seminaria contagiosa, 'disease seeds' that were carried by the wind or communicated by contact with infected objects.

Francesco Redi, in 1699, boiled broth and sealed it in containers proving that maggots did not develop in meat protected from flies and putrefaction did not occur without contamination. This should have disproved spontaneous generation, but John Needham, in 1748, repeated the experiment and saw 'animalcules' in the broth, which must have appeared spontaneously.

The debate about spontaneous generation continued for another century. In 1835, Agostino Bassi, manager of a silkworm estate, conducted an experiment with a silkworm disease, muscarine. A fungus on the dead silkworms could produce the disease when healthy silkworms were incubated with it. Jacob Henle, influenced by Bassi's observations, concluded in 1840 that a living agent that acted as a parasite caused infectious diseases. The theory had been proposed repeatedly since the sixteenth century but remained on the fringes of medical science until after 1870 and the work of the great Frenchman Louis Pasteur (1822-1895). One famous victim of this resistance to the germ theory was the Hungarian physician Ignaz Semmelweis (1818–1865).

In some history books I have seen, it is said that Semmelweis was born in Budapest in the Austro-Hungarian Empire. This is slightly inaccurate since the beautiful city of Budapest, today the capital city of Hungary, was initially two different cities, Buda and Pest, occupying both banks of the river Danube, and they weren't merged until 1873, after Semmelweiss had died. Likewise, the Austrian Empire didn't become the dual monarchy known as the Austro-Hungarian Empire until 1867 (it was formally dissolved after World War I).

In any case, while working in the Imperial capital at the Vienna General Hospital in 1847, Semmelweiss discovered that the frequency of puerperal fever or childbed fever could be drastically reduced by simple hand washing methods with chlorinated lime solutions.

His insight that puerperal fever was transmitted to patients by doctors led to his expulsion from his position and the delay of a discovery that could have saved the lives of tens of thousands of women. He is now regarded as a pioneer of antiseptic procedures, but his ideas didn't gain acceptance until after his death. That Semmelweiss could suffer this rejection even by the middle of the nineteenth century shows how late the germ theory of disease was established.

As Mokyr says, "

Even after the discovery was made, American physicians fiercely resisted it. On the European continent, which was more receptive to techniques based on the body of useful knowledge we call bacteriology, resistance was weaker. Indeed, the idea went back to a much earlier age. The idea of germ-caused infection was first proposed by Girolamo Fracastoro in his De Contagione (1546).

In 1687, Giovanni Bonomo explicitly proposed that diseases were transmitted because minute living creatures he had been able to see through a microscope passed from person to another (Reiser, 1978. p. 72). Bonomo's observations, along with the microscopy of pioneers like Leeuwenhoek, ran into skepticism because they were irreconcilable with accepted humoral doctrine.

Pasteur and Koch's demonstrations of the culpability of bacteria took many years to be accepted, and the opposition of some of the great figures of public medicine at the time, such as the sanitary reformer Max von Pettenkofer and Rudolf Virchow, the founder of cell pathology, is legendary. In New York, well-known doctors walked out of scientific meetings in protest as soon as the issue of bacteriology was raised (Rothstein, 1972, p. 265).The canning of food was invented in the early 1800s by a French confectioner named Nicolas Appert (1749-1841). He placed food in champagne bottles, corked them loosely, immersed them in boiling water and hammered the corks tight. This practice preserved the food for extended periods, but neither he nor his emulators who later perfected the preservation of food in tin-plated canisters knew why this technique worked; it's a textbook case of an applied technology without any theoretical basis. Louis Pasteur knew of Appert's work, but his scientific methods and careful experiments succeeded in convincing many skeptics.

The optimal temperatures for the preservation of various foods with minimal damage to flavor were worked out by two scientists at the Massachusetts Institute of Technology (MIT) in the USA, Samuel Prescott (1872–1962) and William Lyman Underwood (1864–1929) in 1895-96.

Their work represented a milestone in the development of food technology and food science. Appert's method of cooking the food to a temperature far in excess of what is used in pasteurization can easily destroy some of the flavor.

Pasteurization does not intend to kill all microorganisms, only to reduce their number sufficiently to prevent them from causing diseases. Complete sterilization has negative effects on the taste of the food. Pasteur had developed an interest for chemistry and biology and focused on the souring of milk and the fermentation of sugar to alcohol.

He was convinced that the latter was a biological phenomenon. In France, wine is a source of both revenue and national pride. Kennedy again:

Pasteur worked on problems of the wine industry and proved that Mycoderma aceti was the microorganism responsible for souring wine. Furthermore, he demonstrated that heating wine to fifty-five degrees centigrade, which did not damage the wine, killed the organism and prevented the souring.

Eventually, the principle was applied to beer and milk and the term 'Pasteurization' became a common one. The Pasteurizing process has virtually eliminated the risk of tuberculosis from milk without affecting its quality. Henle had argued that fermentation, putrefaction, and disease were related and Pasteur had demonstrated microorganisms, which produced these phenomena, in the air.

The connection was there to be explored. The next step was the study of another silkworm disease, pebrine which was producing serious problems for the industry. Pasteur demonstrated that the cause was a living organism, a protozoan, and discovered its life cycle from moth to egg to chrysalis. On February 19, 1878, he appeared before the French Academy of Medicine to present the germ theory of disease. According to Mokyr,

In terms of its direct impact on human physical well-being, the victory of the germ theory must be counted as one of the most significant technological breakthroughs in history. The bacteriological revolution heralded a concentrated and focused scientific campaign to once and for all identify pathogenic agents responsible for infectious diseases.

Between 1880 and 1900 researchers discovered pathogenic organisms at about the rate of one a year and gradually identified many of the transmission mechanisms, although many mistaken notions survived and a few new ones were created. The age-old debates between contagionists and anti-contagionists and between miasma and anti-miasma theories slowly evaporated, although the belief that 'bad air' was somehow responsible for diseases such as diarrhea was still prevalent in the 1890s.

The refutation of the Aristotelian notion of 'spontaneous generation' of life from lifeless matter by Pasteur demonstrated that bacterial infection was contracted exclusively from a source outside the body. It provided a much wider epistemic base for a large number of household techniques that were thought to prevent disease, thus making them both more effective and more persuasive.The triumph of the germ theory after 1865 was above all a victory of scientific persuasion by forceful personalities. In 1879, Pasteur turned his attention to chicken cholera and anthrax. He injected chickens with an old, "stale" culture of cholera organisms and later found that they were now immune against "strong" cultures.

Anthrax was a common disease in cattle that occasionally affected humans. According to the previous medical paradigm it had been attributed to "rural miasma." The disease was studied by several scholars, among them the German physician Robert Koch (1843-1910).

While serving as a surgeon in the Franco-Prussian war of 1870, which facilitated the unification of Germany under the leadership of Otto von Bismarck (1815–1898), Koch was appointed to an office as district health officer in Posen in modern Poland. Anthrax was endemic in Posen and this gave Koch an opportunity to examine the disease. He learned that anthrax formed spores which were resistant to heat.

According to Michael Kennedy,

Pasteur used samples of Koch's Bacillus anthracis to conduct experiments on attenuation of the virulence of the organism. Finally, he was able to produce a 'weak' form that could be used to produce a vaccine.

On May 5, 1881, he injected twenty-four sheep, a goat and six cattle with the attenuated strain of anthrax at a public demonstration. A similar group was left unexposed. On May 17, a second injection, using a stronger culture, was given to the test animals. On May 31, all animals, inoculated and naïve (the control group), were given an injection of virulent anthrax. By June 2, all the sheep and the goat in the control group were dead and the cattle were sick. The inoculated group was all healthy.

The era of vaccines had begun and medicine was finally able to prevent, if not yet treat, disease. It had taken nearly 100 years since Jenner to develop a second vaccine. Pasteur had been able to produce artificially the attenuated strain of an organism that nature had provided in smallpox/cowpox.In 1880 Pasteur, aided by his assistant Charles Chamberland (1851-1908) and the doctor Pierre Roux (1853–1933), began to study the feared disease rabies, which was (and remains when untreated) almost 100% lethal. He didn't see the organism causing rabies since the virus is too small to be seen in optical microscopes. He injected spinal cord tissue from infected individuals into rabbit brain, which caused infection with an incubation period of six days.

In 1884 he proceeded to test a weakened form of the disease on dogs that later turned out to be immune against virulent rabies. Because of the long incubation period, immunization could be effective even after exposure to rabies, if done quickly.

This vaccine was first used on the 9-year-old Joseph Meister (1876–1940) in July 1885 after the boy was badly mauled by a rabid dog. Trying the vaccine on humans even with a weakened version of the virus was obviously risky, but since the boy had already been infected he faced almost certain death without treatment. The vaccination was a success, and a new vaccine had been introduced.

There are still debates as to whether or not a virus should be considered a living organism since it can only multiply in living cells of other organisms, be that of animals, plants or bacteria.

The Russian biologist Dmitry Ivanovsky (1864-1920) in 1892 and the Dutch microbiologist Martinus Beijerinck (1851-1931) in 1898 both found that a disease of tobacco plants was transmitted by an agent, later called tobacco mosaic virus, small enough to pass through a filter that would not allow the passage of bacteria. Apparently Beijerinck understood that he was dealing with a new kind of infectious agent which he dubbed a virus. He is considered the founder of virology.

Viruses are so small, even compared to bacteria, that they cannot be seen in traditional microscopes. In the 1940s the development of the electron microscope, which due to the much smaller wavelength of electrons vs. that of visible light allows for far greater resolution and magnification than light microscopes, permitted individual virus particles to be seen for the first time. Advances in the second half of the twentieth century and the early years of the twenty-first have revolutionized the study of viruses.

The ruling miasma theory of disease held that diseases such as cholera were caused by a miasma (Greek: "pollution"), a form of "bad air." During the Victorian era, especially between 1820 and 1870, a great sanitarian and hygienic movement started a widespread but unfocused war against dirt based on a vague correlation with disease.

It was believed that filth was a source of disease but that disease spores traveled through odors, which led to a great emphasis on ventilation and refuse removal. This strategy did have some positive effects, although the reason for this was not properly understood. Mokyr explains:

The war against filth, which had eighteenth-century roots, drew new strength and focus from the statistical revolution that grew out of the Enlightenment and led to the development of nineteenth-century epidemiology. It provided data to support the close relation, long suspected, among consumption patterns, personal habits, and disease….

The roots of this movement went back more than a century, especially to the debates around the efficacy of smallpox inoculation procedure, the beneficial effects of breast-feeding, and the bad effects of miasmas (putative disease-causing elements in the atmosphere). The empirical regularities discovered by the statisticians reinforced earlier middle-class notions that cleanliness enhances health.

By the middle of the nineteenth century, those notions were filtering down vertically through the social layers of society. But their persuasiveness was vastly extended by the growing interest in statistics and the analysis of what we today would call 'data' dating to the decades after 1815.

The founding of the Statistical Society of London in 1834 led to an enormous upsurge in statistical work on public health. In Britain, William Farr, William Guy, and Edwin Chadwick were the leaders of this sanitary movement, but it encompassed many others (Flinn, 1965).Lister, Jenner and others used practical measures to deal with diseases caused by microorganisms they did not believe in. The pioneering nurse and statistician Florence Nightingale (1820–1910), a firm believer in the miasmatic theory of disease, placed much emphasis on hospital sanitation.

Between 1853 and 1862, a quarter of the papers read before the Statistical Society of London dealt with public health. Similar establishments existed in other European countries. The sanitarian movement looked for empirical regularities, which often led down blind alleys but sometimes to real advances in epidemiology.

Many social reformers and activists were enthusiastic members of the Statistical Society. Among the great triumphs of this methodology were the discoveries of John Snow and William Budd in the 1850s that water was the transmission mechanism of cholera and typhoid, and in 1878 that milk was a carrier of diphtheria. š In Germany, the founder of modern physiology, Rudolf Virchow, called for more medical statistics: "We will weigh death and life and see where death lies thicker," he insisted. The influential German physician Max von Pettenkofer (1818-1901) fought against the germ theory of disease, yet still advocated public health measures to prevent the spreading of infectious disease in the city of Munich.

The English civil engineer Sir Joseph Bazalgette (1819–1891) played a leading role in improving public health in London during this period. A cholera epidemic in the late 1840s killed thousands of Londoners, and another epidemic struck in 1853, killing thousands more. The medical opinion at the time still held that cholera was caused by foul air, miasma.

The River Thames resembled an open sewer. In 1858, Parliament passed an enabling act to channel London's sewerage system into underground brick sewers, built to such generous scale that they are still in use to this day.

In Paris, Napoléon III (1808–1873) commissioned major works designed to modernize the city. Led by Georges-Eugène Haussmann (1809–1891), the project in the 1850s and 60s changed the face of Paris into a city of wide boulevards, large public parks and a new sewer system. Indirectly, the changes did benefit public hygiene. A little later, the Eiffel Tower was built in 1889, symbolizing the new age.

Paris and London remained two of Europe's leading cities, but the urban hierarchies of the continent did change somewhat between 1750 and 1950. Some cities such as Liverpool, Manchester and Birmingham experienced spectacular growth related to the Industrial Revolution.

The Russian cities Moscow and St. Petersburg were special cases, disproportionately large compared to other cities in the Russian Empire. Sofia, Bulgaria, grew rapidly during the late nineteenth and early twentieth centuries, as did Bucharest, Romania and Budapest.

Berlin was arguably the most spectacular case of all as it grew during the second half of the nineteenth century into one of the most dynamic cities not just in Germany, but in all of Europe. London, Paris and Berlin built underground railroads, as did Budapest, New York City and eventually other cities such as Madrid. In beautiful Barcelona, straight streets blasted through the central slums. The Catalonian city experienced a cultural spring, visually represented by the unique buildings of the architect Antonio Gaudí (1852–1926).

The dirty chaos of early industrial urbanism was not always healthy, but better nutrition and education, especially in the cities, facilitated the spread of new knowledge which improved public health. Technological advances had positive effects on urban areas in the nineteenth and twentieth centuries.

The development of lifts, piped water and gas, electricity, sewer lines, water closets and central heating meant that it was now possible to manage urbanization without decay, and indeed improve the quality of life as well as health. Big cities and national capitals led the way in this reduction in mortality, which took place earlier in Northern and Western Europe than in the South or East.

In the end, the effects of industrialization were felt in every city across the European continent, and eventually across the world. Paul Hohenberg and Lynn Lees explain in The Making of Urban Europe, 1000-1994:

National governments cared more about their capitals, and money was more easily forthcoming there for the massive investments that proper sanitation required. At a time when Paris had already built new water and sewerage systems, the Marseille population still drank polluted water from the Durance River.

In consequence, the Mediterranean port was the site of the last big cholera epidemic in France in 1884, at a time when death rates in Paris had already fallen (W. Lee 1979; Pinkney 1958). Improvement in urban death rates began in central Europe before 1890. Indeed, in Austria and in Bavaria urbanites had a higher life expectancy than did their country cousins by the later 1880s (A. Weber 1899).

Even in southern and eastern Europe, where demographic change set in more slowly, the major cities were far less deadly in 1900 than they had been a century before. In the long run improved life expectancy more than equalized risks between the urban and the rural environment.

By the later nineteenth century towns shifted from being killers to being net producers of people.Yellow fever devastated much of the American South and the Caribbean region in the nineteenth century, but it took some time before the mechanisms of its transmission were understood. As Joel Mokyr writes:

During the cleanliness campaigns of the mid-nineteenth century standing water and open sewage in cities were reduced, and with them the mosquitoes. The decline of the disease was attributed to the disappearance of the stench. Memphis, for example, was free of yellow fever after the sanitation campaign, but since the epistemic base was essentially empty, this experience could not be put to good use elsewhere (Spielman and d'Antonio, 2001, pp. 72-73).

The suspicion that mosquitoes might be involved in the transmission of some diseases had already been raised in 1771 by an Italian physician named Giovanni Lancisi (for the case of malaria), and in 1848 a physician from Mobile, Alabama, Dr. Josiah Nott, extended the idea to yellow fever.

A more detailed hypothesis that the disease was spread by the mosquito Aedes aegypti was put forward by a Cuban doctor, Carlos Finlay, in 1878, but his experiments failed to carry conviction, in part because the notion that insects carried disease was too novel and revolutionary for many physicians to accept (Humphreys, 1992, pp. 35-36). Only in 1900 did Walter Reed demonstrate the infection mechanism by persuasive experimental methods (costing the lives of three volunteers).Another revolution in medicine at this time was the realization that small traces of certain substances are vital to human health and that some crucial substances cannot be manufactured by the body from other nutrients and need to be supplied through the diet. This was coupled with the understanding that some diseases are not caused by bacteria or germs, but by deficiencies of trace elements.

The Japanese naval physician Takaki Kanehiro (1849–1920), who had received education in traditional Chinese medicine as well as modern Western medical science, discovered that the disease beriberi, which represented a serious problem for the Japanese navy at the time, was caused by nutritional deficiency, not by infectious germs.

This was confirmed by the Dutch physician Christiaan Eijkman (1858–1930) in 1897, who demonstrated a link between beriberi and diet. Eijkman received a Nobel Prize in 1929 together with the English biochemist Frederick Hopkins (1861-1947) for their discovery of several vitamins.

The name "vitamin" was introduced by the Polish biochemist Casimir Funk (1884-1967) in 1912. After reading an article by Eijkman he tried to isolate the substance in question, which we now know as vitamin B1. These substances that are vital to human health he called vital amines or vitamines. Most vitamins are obtained with food but a few by other means.

The concept that eating certain types of food can be beneficial to your health had been known since ancient times but remained unspecific, as did most medical knowledge prior to modern times.

The Scottish physician James Lind (1716–1794) conducted the first clinical trial in the British Royal Navy in the mid-eighteenth century to prove that citrus fruits cure scurvy, and published his Treatise on the Scurvy, which recommended using lemons and limes to avoid scurvy, in 1753.

The Dutch East India Company kept citrus trees on the Cape of Good Hope in the seventeenth century, but the knowledge kept being rediscovered and lost for centuries. The active ingredient, which we know as vitamin C, was only detected in the twentieth century by the Hungarian physiologist Albert Szent-Györgyi (1893–1986).

The medical advances of the twentieth century, from the discovery of insulin by the Canadian scientist Frederick Banting (1891–1941) in the early 1920s via the development of the modern intensive care unit to the introduction of the artificial birth-control pill in the 1960s (which had major social and demographic consequences) are simply too numerous to list. I will briefly mention only a few of them here.

Experiments with blood transfusions, the transfer of blood into a person's blood stream, had been carried out for hundreds of years at the cost of many lives, since mixing the blood from different individuals can have potentially lethal consequences. The American surgeon William Stewart Halsted (1852–1922) performed one of the first blood transfusions in the United States in 1881 by giving some of his blood to his sister save her life.

The discovery of human blood groups was made in 1901 by the Austrian physician Karl Landsteiner (1868–1943). He developed the ABO blood group system, the most important (but by no means the only) blood type system in use today. Other early pioneers in the field include the American Alexander S. Wiener (1907-1976) and the Czech serologist Jan Janský (1873–1921).

The new scientific understanding of blood groups made blood transfusions far safer and enabled the development of blood banks. Along with other advances in surgery and antiseptics, this gradually made possible organ transplant of vitals organs such as kidneys and livers.

The first successful human-to-human heart transplant was achieved in December 1967 in Cape Town by Christiaan Barnard (1922–2001), the son of a minister in the Dutch Reformed Church in South Africa. The American physician Norman Shumway (1923–2006) contributed some of the research leading to the first human heart transplants.

Another major advance in the twentieth century was the discovery of antibiotics, which are natural substances. One of the first recorded observations of penicillin was made by the Irish physicist John Tyndall (1820–1893) who in 1875 reported to the Royal Society in London that it killed bacteria, but he then passed on to other matters.

In 1896 the French medical student Ernest Duchesne (1874–1912) commented on the antagonism between the Penicillium notatum mold and bacteria, but he didn't follow this insight up. The Costa Rican scientist Clodomiro Picado Twight (1887-1944), who also did research on snakes and anti-venom serums, did work on penicillin during the First World War, and in 1925 the bacteriologist André Gratia (1893–1950) of the University of Liège in Belgium reported that a substance produced by Penicillium could dissolve anthrax bacilli, but again there was no follow-up.

The general credit for discovering penicillin is usually granted to the Scottish biologist Alexander Fleming (1881–1955), who discovered the substance by accident in 1928. He published articles on the subject in 1929 and 1932, but then abandoned the subject.

A bacteriologist named Cecil Paine obtained a sample of Penicillium notatum from Fleming, made broth cultures and applied it to several test subjects with infections who responded to the treatment. He reported these results to the Australian scholar Howard Florey (1898–1968).

An important breakthrough came with the German bacteriologist Gerhard Domagk (1895–1964), who found the first effective drug against infections caused by bacteria in 1935.

Ernst Boris Chain (1906–1979), a Jew and refugee from Nazi Germany, went to Florey with a suggestion that they investigated the anti-bacterial properties of Fleming's discovery. They had access to one of Fleming's cultures and in 1939 led a team of researchers at the University of Oxford in England, made tests on mice and eventually found a stable form suitable for practical use by freeze-drying the penicillin. Though mass-production remained a challenge, penicillin was available to the Allied forces during the final phases of the Second World War. Fleming, Chain and Florey shared a Nobel Prize in 1945 for the discovery.

Charles Darwin's On the Origin of Species, published in 1859, triggered a massive debate about evolutionary biology, but the principles behind inheritance were not worked out by Mr. Darwin.

This was done by Gregor Mendel (1822 –1884), a German-speaking priest born in Brünn or Brno, the second-largest city of what is today the Czech Republic but was then a part of the Austrian Empire. He was a monk and a trained scientist who had studied at the University of Vienna. Although he is considered the "father of genetics" he did not coin the term "gene."

This was introduced by the Dutch botanist Hugo de Vries (1848-1935) as "pangen" and later abbreviated by scholar Wilhelm Johannsen (1857-1927) from Denmark to "gene" ("gen" in Danish). Mendel studied the laws of inheritance by cultivating and testing tens of thousands of pea plants between 1856 and 1863. He demonstrated that the inheritance of traits follows specific laws which we now call Mendelian inheritance, yet his work did at first not gain widespread attention when it was published in the 1860s.

According to John Gribbin,

Mendel had shown conclusively that inheritance works not by blending characteristics from the two parents, but by taking individual characteristics from each of them.

By the early 1900s, it was clear (from the work of people such as William Sutton at Columbia University) that the genes are carried on the chromosomes, and that chromosomes come in pairs, one inherited from each parent. In the kind of cell division that makes sex cells, these pairs are separated, but only (we now know) after chunks of material have been cut out of the paired chromosomes and swapped between them, making new combinations of genes to pass on to the next generation.

Mendel's discoveries were presented to a largely uncomprehending Natural Science Society in Brünn (few biologists had any understanding of statistics in those days) in 1865, when he was 42 years old. The papers were sent out to other biologists, with whom Mendel corresponded, but their importance was not appreciated at the time. In 1868 Mendel became Abbot at his monastery and no longer had time to continue his scientific work. The rediscovery of the Mendelian laws of inheritance in the early twentieth century, combined with the identification of chromosomes, provided the keys to understanding how evolution works at the molecular level. This has provided us with new insights into hereditary diseases or genetic disorders, among other things.

In the twenty-first century Western hospitals contain equipment our ancestors could scarcely have imagined, like laser eye surgery or CAT-scan machines. The evolution of nanotechnology carries much potential for applications in future medicine.

However, perhaps the greatest of all revolutions has not been the development of new machines but of insights into the world of proteins, chromosomes, cells and eventually deoxyribonucleic acid, or DNA, which contains the genetic instructions that make us who we are.

In 1953, DNA's structure as a double helix had been established by the American molecular biologist James D. Watson (b. 1928), the English scientist Francis Crick (1916–2004) and the New Zealand-born Maurice Wilkins (1916–2004), who all shared the 1962 Nobel Prize for this achievement. The creation of molecular biology may well be viewed as the most significant medical event of the twentieth century by future generations, even though its full effects have not yet been seen.

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