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Vesalius and the science of anatomy: 1533-1543

A young medical student, born in Brussels and known to history as Vesalius, attends anatomy lectures in the university of Paris. The lecturer explains human anatomy, as revealed by Galen more than 1000 years earlier, while an assistant points to the equivalent details in a dissected corpse. Often the assistant cannot find the organ as described, but invariably the corpse rather than Galen is held to be in error.

Vesalius decides that he will dissect corpses himself and trust to the evidence of what he finds. His approach is highly controversial. But his evident skill leads to his appointment in 1537 as professor of surgery and anatomy at the university of Padua.

In 1540 Vesalius gives a public demonstration of the inaccuracies of Galen's anatomical theories, which are still the orthodoxy of the medical profession.

Galen did many of his experiments on apes. Vesalius now has on display - for comparison - the skeletons of a human being and of an ape.

Vesalius is able to show that in many cases Galen's observations are indeed correct for the ape, but bear little relation to the man. Clearly what is needed is a new account of human anatomy.

Vesalius sets himself the task of providing it, illustrated in a series of dissections and drawings. He has at his disposal a method, relatively new in Europe, of ensuring accurate distribution of an image in printed form - the art of the woodcut. His studies inaugurate the modern science of anatomy.

At Basel, in Switzerland, Vesalius publishes in 1543 his great work - De humani corporis fabrica (The Structure of the Human Body). There are seven volumes including numerous magnificent woodcut illustrations. The book is an immediate success, though naturally it enrages the traditionalists who follow Galen. Galen's theories have, after all, the clear merit of seniority. They are by now some 1400 years old.

But for those willing to look with clear eyes, the plates in Vesalius's volumes are a revelation. For the first time human beings can peer beneath their own skins, in these strikingly clear images of what lies hidden.

Surgery: 16th - 17th century

In an age before anaesthetics, surgery is inevitably a limited branch of medicine. It is also considered a rather lowly craft, despised by doctors whose reputation is based on their knowledge of the approved authorities rather than clinical skills. Surgeons are linked with barbers, who also require sharp instruments to practise their trade.

The most frequent use of the surgeon's knife is to open patients' veins for blood-letting, also known as bleeding. This is the treatment most often prescribed by the learned physicians, because Galen has pronounced that fevers and apoplexy result from an excessive build-up of blood in the system.

However there is one area where surgeons are increasingly in demand from the 16th century, and where they rapidly learn and acquire new skills - on the battlefield. The arrival of artillery and muskets alters the nature of wounds. Instead of the clean cut inflicted by sword thrust or pike, there are now gaping holes of torn flesh and shattered bones.

The greatest surgeon of the 16th century, Ambroise Paré, rises from the humble status of a barber's apprentice to become surgeon to the kings of France, and does so mainly through knowledge acquired in the treatment of war wounds.

Paré publishes in 1545 the first account of his military experiences under the title La Methode de traicter les playes faictes par Hacquebutes, et aultres bastons a feu (The Method of treating wounds caused by Arquebuses and other firearms).

His most significant discovery is that the traditional treatment of any gunshot wound (violently cauterizing it with boiling oil because it is assumed to be poisoned by the gunpowder), does considerable extra harm to the patient. Paré achieves much greater success by simply dressing the wounds with a mixture of egg yolk, oil of roses and turpentine.

Paré also makes advances in the use of ligatures for sealing blood vessels to staunch the flow of blood. As many as fifty-three are needed after the amputation of a thigh. Amputation is the only form of major surgery which surgeons of this period are able to practise. The other major operations of modern surgery, by incision into the abdomen or other cavities of the body, were at the time too dangerous to perform.

There is one exception to this - the removal of stones from the bladder. A medical text by Celsus, writing in Rome in the 1st century AD, reveals that this operation is performed in classical times. It is relatively easy to achieve because a large stone can be pressed by the surgeon's finger hard against the patient's skin for incision and extraction.

A famous patient, Samuel Pepys, is 'cut for the stone' in London on 26 March 1658. The operation is carried out by Thomas Hollyer of St Thomas's Hospital. It takes place not in the hospital but in a large room in a house of one of Pepys's relations. It needs to be large. The whole family gathers in case the event turns out to be a death scene.

With no effective pain-killer available (Pepys is offered rose water with white of egg and liquorice), the speed of the surgeon is all-important. The record for this operation in the next century is fifty-four seconds. Pepys survives, to begin his diary two years later. He has a cabinet built to display the two-ounce stone, and resolves to keep March 26 as a festival each year.

Harvey and the circulation of the blood: 1628

A book is published in 1628 which provides one of the greatest breakthroughs in the understanding of the human body - indeed perhaps the greatest until the discovery of the structure of DNA in the 20th century.

The book consists of just fifty-two tightly argued pages. Its text is in Latin. Its title is Exercitatio anatomica de motu cordis et sanguinis in animalibus ('The Anatomical Function of the Movement of the Heart and the Blood in Animals'). Its author is William Harvey. In this book he demonstrates beyond any reasonable doubt an entirely new concept. Blood, he shows, does not drift in the body in any sort of random ebb and flow. Instead it is pumped endlessly round a very precise circuit.

Until now it has been assumed that the blood in arteries and the blood in veins are different in kind. It is well known that they are of a different colour, and there have been many theories as to what each supply of blood does.

The most commonly held belief is that arterial blood carries some sort of energy connected with air to the body (not far from the truth), and that blood in the veins distributes food from the liver (less accurate).

By a long series of dissections (from dogs and pigs down to slugs and oysters), and by a process of logical argument, Harvey is able to prove that the body contains only a single supply of blood; and that the heart is a muscle pumping it round a circuit.

This circuit, as he can demonstrate, brings the blood up from the veins into the right ventricle of the heart; sends it from there through the lungs to the left ventricle of the heart; and then distributes it through the arteries back to the various regions of the body.

After much initial opposition, Harvey's argument eventually convinces most of his contemporaries. But there are two missing ingredients. His theory implies that there must be a network of tiny blood vessels bringing the blood from the arterial system to the venous system and completing the circuit. But his dissections are not adequate to demonstrate this. It is not till four years after his death that Marcello Malpighi observes the capillaries.

And Harvey is unable to explain why the heart should circulate the blood. That explanation will have to await the discovery of oxygen.

Malpighi and the microscope: 1661

Marcello Malpighi, a lecturer in theoretical medicine at the university of Bologna, has been pioneering the use of the microscope in biology.

One evening in 1661, on a hill near Bologna, he uses the setting sun as his light source, shining it into his lens through a thin prepared section of a frog's lung. In the enlarged image it is clear that the blood is all contained within little tubes.

Malpighi thus becomes the first scientist to observe the capillaries, the tiny blood vessels in which blood circulates through flesh . They are so fine, and so numerous, that each of our bodies contains more than 100,000 kilometres of these microscopic ducts.

With their discovery, the missing link in Harvey's circulation of the blood has been found. For the capillaries are literally the link through which oxygen-rich blood from the arteries first delivers its energy to the cells of the body and then finds its way back to the veins to be returned to the heart.

Blood transfusion: 1665-1670

At a meeting of the recently established Royal Society in London, on 14 November 1665, an experiment is made in transferring blood from one dog to another. The artery of a small mastiff is joined by a quill to the vein of a spaniel. Another of the spaniel's veins is opened to let out an equivalent amount of its own blood.

The mastiff bleeds to death in front of the Society. The spaniel is produced at the equivalent meeting a week later and is found to be in fine health.

Two years later, in France, a much more ambitious step is taken along these same lines. Jean Baptiste Denis, royal physician to Louis XIV, conducts a bold experiment in 1667 in Paris. In an attempt to save the life of a 15-year-old boy, weakened by too much blood-letting, he inserts into his veins, through a quill, about half a pint of the blood of a lamb.

Contemporary reports say that the condition of the boy is greatly improved.

Later in the same year, following this impressive example from Paris, the Royal Society in London becomes more bold in its experiments. Arthur Coga, a divinity student from Cambridge who is said to be slightly 'frantic', is hired for a transfusion. Half a pint of sheep's blood is passed into his vein. The scientists hope that this will cool his own blood and thus make him less frantic.

Opinions differ as to whether this desirable effect is achieved. When asked why he has received sheep's blood, rather than that of any other creature, the divinity student replies that it is because Christ is the Lamb of God.

A week later Mr Coga addresses the Society in Latin and declares that he feels much better. Later on the same day Pepys meets him at dinner and still finds him 'cracked a little in his head'. Pepys is rather shocked to hear that Coga 'had but 20 shillings for his suffering it, and is to have the same again tried on him'. He receives a second transfusion three weeks after the first, and apparently experiences no lasting ill effects.

Pepys says that Coga is the first healthy man to have had the experiment tried upon him, apart from a porter in France hired for the same purpose 'by the virtuosi'. But a disaster in France is about to put an end to this run of experiments.

Following his success in 1667, Jean Baptiste Denis has given blood to several other patients with continuing success. But in 1668, after a third transfusion, one of his patients dies. Denis is sued by the widow. He loses the case, though he is cleared of murder.

The result is that the entire experiment falls into disrepute, after a turmoil of excitement lasting three years. In 1670 a law is passed in France making blood transfusion illegal. For another two centuries no more is heard of it anywhere - until it is again attempted fairly regularly in mid-19th century England, now usually with human blood. But it remains a hazardous procedure until the discovery, in 1900, of the human blood groups.

Inoculation: 17th - 18th century

At some time before the end of the 17th century a bold procedure, possibly practised already for several centuries in parts of Asia, becomes established in Turkish medicine. It is the use of inoculation to protect against the extremely infectious and frequently fatal disease of smallpox.

Inoculation is based on an easily observed medical fact - that those who contact an infectious disease and survive are protected against catching it again. Inoculation is a precautionary measure, though in the case of smallpox a dangerous one.

Pustulent matter from the skin of a lightly infected smallpox victim is rubbed into a fresh scratch in the skin of the person being inoculated, with the intention of inducing a mild attack of the disease. Most of those undergoing the treatment survive and are protected. The unfortunate few die.

The procedure reaches Europe because of a sequence of events in the early 18th century. In 1715 Lady Mary Wortley Montagu, a young beauty and wit in fashionable London, catches smallpox. She survives but is left with disfiguring scars. A year later her husband is appointed ambassador to the court of the Turkish sultan. She accompanies him to Istanbul, together with their three-year-old son.

In Istanbul she sees inoculation successfully carried out. Her own recent experience prompts her to a possibly reckless decision. She submits her infant son to this Turkish procedure. He survives. Back in London, in 1718, Lady Mary has a second child, a daughter. She has this child inoculated in England. She too survives.

With characteristic vigour Lady Mary now begins campaigning for this basic measure of preventive medicine. She has sufficient success for inoculation to become an increasingly common practice in England during the 18th century. But it remains, inevitably, a hazardous one - until Edward Jenner discovers a safer method.

Practical measures: 1752-1785

The middle years of the 18th century are notable for practical advances in medicine, based on close observation by working practitioners. Some of those who record their experiences are at the academic end of the medical profession, others are country doctors paying attention to detail. Their efforts raise the scientific standards of medicine and introduce techniques and drugs of lasting benefit.

An early example is William Smellie, the first obstetrician to make a scientific study of the physical process of childbirth.

From 1741 Smellie gives midwives and medical students in London unprecedented practical lectures on childbirth. He achieves this by offering his services to poor women on condition that his students may attend the birth. In this way he is able to develop a scientific account of the mechanism of labour, describing previously unobserved details - such as how the child's head is adapted for the passage through the pelvic canal.

Smellie publishes his findings in the three-volume Treatises on the Theory and Practice of Midwifery (1752-64). His text provides a new scientific basis for the ancient skills of the midwife.

A similarly thorough groundwork is provided for pathology in a book of 1761. Its author, Giovanni Battista Morgagni, is seventy-nine at the time of publication. He has spent nearly five decades as professor of anatomy at Padua (a post once occupied by Vesalius). During that time Morgagni has kept detailed notes of his dissections of corpses.

This is not new in itself, for there have by now been many published accounts of post-mortem examinations. Morgagni's originality lies in his related notes, describing the symptoms of his patients before they died.

Morgagni's book is De Sedibus et Causis Morborum per Anatomen Indagatis (On the Seats and Causes of Diseases, investigated by Anatomy). It describes 640 post-mortems with the related clinical records. Symptoms from now on can be interpreted as external signs of known internal conditions.

In the year of Morgagni's publication, 1761, a book comes out in Vienna offering the general practitioner a useful new technique in the analysis of a patient's internal condition. It is the work of Leopold Auenbrugger, an Austrian physician employed in a military hospital. Many of his patients have fluid in the chest. To discover how much, he adapts a technique learnt in his childhood.

As a boy Auenbrugger worked in his father's tavern and learnt how to judge the amount of wine in a barrel by tapping on its top. He now finds that the same technique works well on a patient's chest. Auenbrugger has stumbled upon the basic diagnostic technique known as percussion. He describes his findings in 1761 in Novum Inventum (New Invention).

Auenbrugger's process is disregarded at first by the medical profession. It becomes of more evident use after an invention of half a century later - that of the stethoscope.

Two important developments later in the 18th century are the result of intelligent observation by general practitioners in England. William Withering notices that his country patients use an extract of herbs to alleviate dropsy. By experiment he establishes that the active ingredient is the foxglove. In his Account of the Foxglove (1785) Withering gives clinical details of how to prescribe extract of foxglove, or digitalis, in the treatment of dropsy and hints that it may be of use for heart disease (for which it remains an important drug to this day).

An even more dramatic result of country observations is achieved in the following decade by Edward Jenner.

Jenner and vaccination: 1796-1798

Working as a country doctor in the Gloucestershire village of Berkeley, Edward Jenner is aware of a local theory that people who have suffered a mild form of pox - caught from the infected udders of cows - never catch the much more dangerous smallpox.

Cowpox is a relatively rare disease, unrecognized at the time by the medical profession, and it is not until 1796 that Jenner has an opportunity to test this theory of immunity. In that year a dairymaid develops the symptoms. Jenner takes material from an eruption on her hand and (using a thorn) inoculates an 8-year-old boy, James Phipps, with the substance. Phipps develops cowpox and soon recovers.

The principle of inoculation has become well established since the efforts of Lady Mary Wortley Montagu to encourage the use of infected matter from smallpox victims as a preventive measure. Six weeks after the cowpox inoculation, Jenner gives James Phipps a conventional smallpox inoculation. The expectation would be that he develops a mild attack of smallpox, survives it and becomes immune. In the event, as Jenner hopes, Phipps shows no sign at all of being infected by the smallpox virus.

Continuing his experiments, Jenner proves that even in a long line of inoculation (taking new vaccine from each successive patient suffering from cowpox) the procedure still confers immunity.

Jenner publishes his findings in 1798 in the splendidly titled An Inquiry into the Causes and Effects of the Variolae Vaccinae, a disease discovered in some of the Western Counties of England, particularly Gloucestershire, and known by the name of Cow Pox.

Variolae Vaccinae, meaning literally 'smallpox of cows', is Jenner's scholarly name for cowpox. The phrase soon provides the word vaccination (initially coined in France as a term of mockery) for this new form of inoculation against smallpox. After some initial opposition from the medical establishment, vaccination proves its merits and the use of it rapidly spreads. As early as 1807 it is made compulsory in Bavaria (though not till 1853 in Britain).

In 1806 the president of the USA, Thomas Jefferson, writes to Jenner: 'Future generations will know by history only that the loathsome smallpox existed and by you has been extirpated.' He is right, but the process takes longer than the president probably expects - even though the immediate effects are impressive. In Britain the annual death rate from smallpox falls during the 19th century from about 2000 per million to well under 100. But diseases are difficult to extirpate on a worldwide basis.

Nevertheless smallpox is the first disease with which that aim is eventually achieved. After intensive international vaccination programmes, there is by 1980 no case of smallpox on the planet.

Sections are as yet missing at this point.

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