- medicine, history of
Introductionthe development of the prevention and treatment of disease from prehistoric and ancient times to the 20th century.Medicine and surgery before 1800Primitive (primitive culture) medicine and folkloreUnwritten history is not easy to interpret, and, although much may be learned from a study of the drawings, bony remains, and surgical tools of early man, it is difficult to reconstruct his mental attitude toward the problems of disease and death. It seems probable that humans, as soon as they had reached the stage of reasoning, discovered, by the process of trial and error, which plants might be used as foods, which of them were poisonous, and which of them had some medicinal value. Folk medicine or domestic medicine, consisting largely in the use of vegetable products, or herbs, originated in this fashion and still persists.But that is not the whole story. Man did not at first regard death and disease as natural phenomena. Common maladies, such as colds or constipation, were accepted as part of existence and dealt with by means of such herbal remedies as were available. Serious and disabling diseases, however, were placed in a very different category. These were of supernatural origin. They might be the result of a spell cast upon the victim by some enemy, visitation by a malevolent demon, or the work of an offended god (supernaturalism) who had either projected some object—a dart, a stone, a worm—into the body of the victim or had abstracted something, usually the soul of the patient. The treatment then applied was to lure the errant soul back to its proper habitat within the body or to extract the evil intruder, be it dart or demon, by counterspells, incantations, potions, suction, or other means.One curious method of providing the disease with means of escape from the body was by making a hole, 2.5 to five centimetres across, in the skull of the victim—the practice of trepanning, or trephining. Trepanned skulls of prehistoric date have been found in Britain, France, and other parts of Europe and in Peru. Many of them show evidence of healing and, presumably, of the patient's survival. The practice still exists among primitive people in parts of Algeria, in Melanesia, and perhaps elsewhere, though it is fast becoming extinct.magic and religion played a large part in the medicine of prehistoric or primitive man. Administration of a vegetable drug or remedy by mouth was accompanied by incantations, dancing, grimaces, and all the tricks of the magician. Therefore, the first doctors, or “medicine men,” were witch doctors or sorcerers. The use of charms and talismans, still prevalent in modern times, is of ancient origin.Apart from the treatment of wounds and broken bones, the folklore of medicine is probably the most ancient aspect of the art of healing, for primitive physicians showed their wisdom by treating the whole person, soul as well as body. Treatments and medicines that produced no physical effects on the body could nevertheless make a patient feel better when both medicine man and patient believed in their efficacy. This so-called placebo effect is applicable even in modern clinical medicine.The ancient Middle East and EgyptThe establishment of the calendar and the invention of writing marked the dawn of recorded history. The clues to early knowledge are scanty, consisting of clay tablets bearing cuneiform signs and seals that were used by physicians of ancient Mesopotamia (Mesopotamia, history of). In the Louvre there is preserved a stone pillar on which is inscribed the Code of Hammurabi (Hammurabi, Code of), who was a Babylonian (Babylonia) king of the 18th century BC. This code includes laws relating to the practice of medicine, and the penalties for failure were severe. For example, “If the doctor, in opening an abscess, shall kill the patient, his hands shall be cut off”; if, however, the patient was a slave, the doctor was simply obliged to supply another slave.The Greek historian Herodotus stated that every Babylonian was an amateur physician, since it was the custom to lay the sick in the street so that anyone passing by might offer advice. divination, from the inspection of the liver of a sacrificed animal, was widely practiced to foretell the course of a disease. Little else is known regarding Babylonian medicine, and the name of not a single physician has survived.When the medicine of ancient Egypt (Egypt, ancient) is examined, the picture becomes clearer. The first physician to emerge is Imhotep, chief minister to King Djoser in the 3rd millennium BC, who designed one of the earliest pyramids, the Step Pyramid at Ṣaqqārah, and who was later regarded as the Egyptian god of medicine and identified with the Greek god Asclepius. Surer knowledge comes from the study of Egyptian papyri, especially the Ebers (Ebers papyrus) and Edwin Smith papyri (Edwin Smith papyrus) discovered in the 19th century. The former is a list of remedies, with appropriate spells or incantations, while the latter is a surgical treatise on the treatment of wounds and other injuries.Contrary to what might be expected, the widespread practice of embalming the dead body did not stimulate study of human anatomy. The preservation of mummies has, however, revealed some of the diseases suffered at that time, including arthritis, tuberculosis of the bone, gout, tooth decay, bladder stones, and gallstones; there is evidence too of the parasitic disease schistosomiasis, which remains a scourge still. There seems to have been no syphilis or rickets.The search for information on ancient medicine leads naturally from the papyri of Egypt to Hebrew (Judaism) literature. Though the Bible contains little on the medical practices of Old Testament times, it is a mine of information on social and personal hygiene. The Jews were indeed pioneers in matters of public health.Douglas James Guthrie Philip RhodesTraditional medicine and surgery in the OrientIndian medicine has a long history. Its earliest concepts are set out in the sacred writings called the Vedas (Veda), especially in the metrical passages of the Atharvaveda, which may possibly date as far back as the 2nd millennium BC. According to a later writer, the system of medicine called Āyurveda was received by a certain Dhanvantari from Brahma, and Dhanvantari was deified as the god of medicine. In later times his status was gradually reduced, until he was credited with having been an earthly king who died of snakebite.The period of Vedic medicine lasted until about 800 BC. The Vedas are rich in magical practices for the treatment of diseases and in charms for the expulsion of the demons traditionally supposed to cause diseases. The chief conditions mentioned are fever (takman), cough, consumption, diarrhea, dropsy, abscesses, seizures, tumours, and skin diseases (including leprosy). The herbs recommended for treatment are numerous.The golden age of Indian medicine, from 800 BC until about AD 1000, was marked especially by the production of the medical treatises known as the Caraka-saṃhitā and Suśruta-saṃhitā, attributed, respectively, to Caraka, a physician, and Suśruta, a surgeon. Estimates place the Caraka-saṃhitā in its present form as dating from the 1st century AD, although there were earlier versions. The Suśruta-saṃhitā probably originated in the last centuries BC and had become fixed in its present form by the 7th century AD. Of somewhat lesser importance are the treatises attributed to Vagbhata. All later writings on Indian medicine were based on these works.Because Hindus (Hinduism) were prohibited by their religion from cutting the dead body, their knowledge of anatomy was limited. The Suśruta-saṃhitā recommends that a body be placed in a basket and sunk in a river for seven days. On its removal the parts could be easily separated without cutting. As a result of these crude methods, the emphasis in Hindu anatomy was given first to the bones and then to the muscles, ligaments, and joints. The nerves, blood vessels, and internal organs were very imperfectly known.The Hindus believed that the body contains three elementary substances, microcosmic representatives of the three divine universal forces, which they called spirit (air), phlegm, and bile (comparable to the humours (humour) of the Greeks). Health depends on the normal balance of these three elementary substances. The seven primary constituents of the body—blood, flesh, fat, bone, marrow, chyle, and semen—are produced by the action of the elementary substances. Semen was thought to be produced from all parts of the body and not from any individual part or organ.Both Caraka and Suśruta state the existence of a large number of diseases (Suśruta says 1,120). Rough classifications of diseases are given. In all texts “fever,” of which numerous types are described, is regarded as important. Phthisis (wasting disease, especially pulmonary tuberculosis) was apparently prevalent, and the Hindu physicians knew the symptoms of cases likely to terminate fatally. smallpox was common, and it is probable that smallpox inoculation was practiced.Hindu physicians employed all five senses in diagnosis. Hearing was used to distinguish the nature of the breathing, alteration in voice, and the grinding sound produced by the rubbing together of broken ends of bones. They appear to have had a good clinical sense, and their discourses on prognosis contain acute references to symptoms that have grave import. Magical beliefs still persisted, however, until late in the classical period; thus, the prognosis could be affected by such fortuitous factors as the cleanliness of the messenger sent to fetch the physician, the nature of his conveyance, or the types of persons the physician met on his journey to the patient.Dietetic treatment was important and preceded any medicinal treatment (therapeutics). Fats (nutrition, human) were much used, internally and externally. The most important methods of active treatment were referred to as the “five procedures”: the administration of emetics, purgatives, water enemas, oil enemas, and sneezing powders. Inhalations were frequently administered, as were leeching, cupping, and bleeding.The Indian materia medica was extensive and consisted mainly of vegetable drugs (drug), all of which were from indigenous plants. Caraka knew 500 medicinal plants, and Suśruta knew 760. But animal remedies (such as the milk of various animals, bones, gallstones) and minerals (sulfur, arsenic, lead, copper sulfate, gold) were also employed. The physicians collected and prepared their own vegetable drugs. Among those that eventually appeared in Western pharmacopoeias were cardamom and cinnamon.As a result of the strict religious beliefs of the Hindus, hygienic measures were important in treatment. Two meals a day were decreed, with indications of the nature of the diet, the amount of water to be drunk before and after the meal, and the use of condiments. Bathing and care of the skin were carefully prescribed, as were cleansing of the teeth with twigs from named trees, anointing of the body with oil, and the use of eyewashes.In surgery, ancient Hindu medicine reached its zenith. Operations performed by Hindu surgeons included excision of tumours, incision and draining of abscesses, punctures to release fluid in the abdomen, extraction of foreign bodies, repair of anal fistulas, splinting of fractures, amputations, cesarean sections, and stitching of wounds.A broad array of surgical instruments were used. According to Suśruta the surgeon should be equipped with 20 sharp and 101 blunt instruments of various descriptions. The instruments were largely of steel. Alcohol seems to have been used as a narcotic during operations, and bleeding was stopped by hot oils and tar.In two types of operations especially, the Hindus were outstanding. Stone in the bladder (urinary bladder) (vesical calculus) was common in ancient India, and the surgeons frequently removed the stones by lateral lithotomy. They also introduced plastic surgery. Amputation of the nose was one of the prescribed punishments for adultery, and repair was carried out by cutting from the patient's cheek or forehead a piece of tissue of the required size and shape and applying it to the stump of the nose. The results appear to have been tolerably satisfactory, and the modern operation is certainly derived indirectly from this ancient source. Hindu surgeons also operated on cataracts by couching, or displacing the lens to improve vision.The Chinese system of medicine is of great antiquity and is independent of any recorded external influences. According to legend, Emperor Huang Ti (the Yellow Emperor (Huangdi)) wrote the canon of internal medicine called the Nei ching in the 3rd millennium BC; but there is some evidence that in its present form it dates from no earlier than the 3rd century BC. Most of the Chinese medical literature is founded on the Nei ching, and it is still regarded as a great authority. Other famous works are the Mo ching (known in the West as the “Pulse Classic”), composed about AD 300; and the Golden Mirror, a compilation, made about AD 1700, of medical writings of the Han dynasty (202 BC–AD 220). European medicine began to obtain a footing in China early in the 19th century, but the native system is still widely practiced.Basic to traditional Chinese medicine is the dualistic cosmic theory of the yin and the yang (yinyang). The yang, the male principle, is active and light and is represented by the heavens; the yin, the female principle, is passive and dark and is represented by the earth. The human body, like matter in general, is made up of five elements (wuxing): wood, fire, earth, metal, and water. With these are associated other groups of five, such as the five planets, the five conditions of the atmosphere, the five colours, and the five tones. Health, character, and the success of all political and private ventures are determined by the preponderance, at the time, of the yin or the yang; and the great aim of ancient Chinese medicine is to control their proportions in the body.The teachings of the religious sects forbade the mutilation of the dead human body; hence traditional anatomy rests on no sure scientific foundation. One of the most important writers on anatomy, Wang Ch'ing-jen, gained his knowledge from the inspection of dog-torn children who had died in a plague epidemic in AD 1798. Traditional Chinese anatomy is based on the cosmic system, which postulates the presence of such hypothetical structures as the 12 channels and the three so-called burning spaces. The body contains five organs (heart, lungs, liver, spleen, and kidneys), which store up but do not eliminate; and five viscera (such as the stomach, intestines, gallbladder, and bladder), which eliminate but do not store up. Each organ is associated with one of the planets, colours, tones, smells, and tastes. There are 365 bones and 365 joints in the body.According to the physiology of traditional Chinese medicine, the blood vessels contain blood and air, in proportions varying with those of the yin and the yang. These two cosmic principles circulate in the 12 channels and control the blood vessels and hence the pulse. The Nei ching says that “the blood current flows continuously in a circle and never stops. It may be compared to a circle without beginning or end.” On this insubstantial evidence it has been claimed that the Chinese anticipated Harvey's discovery of the circulation of the blood. Traditional Chinese pathology is also dependent on the theory of the yin and the yang; this led to an elaborate classification of diseases in which most of the types listed are without scientific foundation.In diagnosis, detailed questions are asked about the history of the illness and about such things as the patient's taste, smell, and dreams. Conclusions are drawn from the quality of the voice, and note is made of the colour of the face and of the tongue. The most important part of the investigation, however, is the examination of the pulse. Wang Shu-ho, who wrote the “Pulse Classic,” lived in the 3rd century BC, and innumerable commentaries were written on his work. The pulse is examined in several places, at different times, and with varying degrees of pressure. The operation may take as long as three hours. It is often the only examination made, and it is used both for diagnosis and for prognosis. Not only are the diseased organs ascertained but the time of death or recovery may be foretold.The Chinese materia medica has always been extensive and consists of vegetable, animal (including human), and mineral remedies. There were famous herbals from ancient times; but all these, to the number of about 1,000, were embodied by Li Shih-chen in the compilation of Pen-ts'ao kang-mu (the “Great Pharmacopoeia”) in the 16th century AD. This work, in 52 volumes, has been frequently revised and reprinted and is still authoritative. The use of drugs is mainly to restore the harmony of the yin and the yang and is also related to such matters as the five organs, the five planets, and the five colours. The art of prescribing is therefore complex.Among the drugs taken over by Western medicine from the Chinese are rhubarb, iron (for anemia), castor oil, kaolin, aconite, camphor, and Cannabis sativa (Indian hemp). Chaulmoogra oil was used by the Chinese for leprosy from at least the 14th century, and about a century ago it began to be used for this purpose by Western physicians. The herb mahuang (Ephedra vulgaris) has been used in China for at least 4,000 years, and the isolation of the alkaloid ephedrine from it has greatly improved the Western treatment of asthma and similar conditions.The most famous and expensive of Chinese remedies is ginseng. Western analysis has shown that it has diuretic and other properties but is of doubtful value. In recent years reserpine, the active principle of the Chinese plant Rauwolfia (Rauvolfia), has been isolated; it is now effectively used in the treatment of high blood pressure and some emotional and mental conditions.Hydrotherapy is probably of Chinese origin, since cold baths were used for fevers as early as 180 BC. The inoculation of smallpox matter, in order to produce a mild but immunizing attack of the disease, was practiced in China from ancient times and came to Europe about 1720. Another treatment is moxibustion (moxa treatment), which consists in making a small, moistened cone (moxa) of powdered leaves of mugwort, or wormwood (Artemisia species), applying it to the skin, igniting it, and then crushing it into the blister so formed. Other substances are also used for the moxa. Dozens of these are sometimes applied at one sitting. The practice is often associated with acupuncture.Acupuncture consists of the insertion into the skin and underlying tissues of a metal needle, either hot or cold. The theory is that the needle affects the distribution of the yin and the yang in the hypothetical channels and burning spaces of the body. The site of the insertion is chosen to affect a particular organ or organs. The practice of acupuncture dates from before 2500 BC and is peculiarly Chinese. Little of practical importance has been added since that date, although there have been many well-known treatises on the subject.A bronze model, c. AD 860, shows the hundreds of specified points for the insertion of the needle; this was the forerunner of countless later models and diagrams. The needles used are three to 24 centimetres (about one to nine inches) in length. They are often inserted with considerable force and after insertion may be agitated or screwed to the left or right. Acupuncture, often combined with moxibustion, is still widely used for many diseases, including fractures. Recently people in the Western world have turned to acupuncturists for relief from pain and other symptoms. There is some speculation that the treatment may trigger the brain to release morphinelike substances called endorphins, which presumably reduce the feeling of pain and its concomitant emotions.The most interesting features of Japanese medicine are the extent to which it was derivative and the rapidity with which, after a slow start, it became westernized and scientific. In the early pre-Christian Era disease was regarded as sent by the gods or produced by the influence of evil spirits. Treatment and prevention were based largely on religious practices, such as prayers, incantations, and exorcism; at a later date drugs and bloodletting were also employed.Beginning in AD 608, when young Japanese physicians were sent to China for a long period of study, Chinese influence on Japanese medicine was paramount. In 982, Tamba Yasuyori completed the 30-volume Ishinhō, the oldest Japanese medical work still extant. This work discusses diseases and their treatment, classified mainly according to the affected organs or parts. It is based entirely on older Chinese medical works, with the yin and yang concept underlying the theory of disease causation.In 1570 a 15-volume medical work was published by Menase Dōsan, who also wrote at least five other works. In the most significant of these, the Keitekishū (a manual of the practice of medicine, 1574), diseases—or sometimes merely symptoms—are classified and described in 51 groups; the work is unusual in that it includes a section on the diseases of old age. Another distinguished physician and teacher of the period, Nagata Tokuhun, whose important books were the I-no-ben (1585) and the Baika mujinzo (1611), held that the chief aim of the medical art was to support the natural force, and consequently that it was useless to persist with stereotyped methods of treatment unless the physician had the cooperation of the patient.European medicine was introduced into Japan in the 16th century by Jesuit missionaries and again in the 17th century by Dutch physicians. Translations of European books on anatomy and internal medicine were made in the 18th century, and in 1836 an influential Japanese work on physiology appeared. In 1857 a group of Dutch-trained Japanese physicians founded a medical school in Edo (later Tokyo) that is regarded as the beginning of the medical faculty of the Imperial University of Tokyo (Tokyo, University of).During the last third of the 18th century it became government policy to westernize Japanese medicine, and great progress was made in the foundation of medical schools and the encouragement of research. Important medical breakthroughs by the Japanese followed, among them the discovery of the plague bacillus in 1894, the discovery of a dysentery bacillus in 1897, the isolation of adrenaline (epinephrine) in crystalline form in 1901, and the first experimental production of a tar-induced cancer in 1918.E. Ashworth Underwood Philip RhodesThe roots of Western medicineEarly GreeceThe transition from magic to science was a gradual process that lasted for centuries, and there is little doubt that ancient Greece (ancient Greek civilization) inherited much from Babylonia and Egypt, and even India and China. Twentieth-century readers of the Homeric tales the Iliad and the Odyssey may well be bewildered by the narrow distinction between gods (Greek religion) and men among the characters and between historical fact and poetic fancy in the story. Two characters, the military surgeons Podaleirius and Machaon, are said to have been sons of Asclepius, the god of medicine. The divine Asclepius may have originated in a human Asclepius who lived about 1200 BC and is said to have performed many miracles of healing.Asclepius was worshiped in hundreds of temples throughout Greece, the remains of which may still be seen at Epidaurus, Cos, Athens, and elsewhere. To these resorts, or hospitals, sick persons went for the healing ritual known as incubation, or temple sleep. They lay down to sleep in the dormitory, or abaton, and were visited in their dreams by Asclepius or by one of his priests, who gave advice. In the morning the patient often is said to have departed cured. There are at Epidaurus many inscriptions recording cures, though there is no mention of failures or deaths.Diet, baths, and exercises (exercise) played their part in the treatment, and it would appear that these temples were the prototype of modern health resorts. Situated in a peaceful spot, with gardens and fountains, each had its theatre for amusements and its stadium for athletic contests. The cult of incubation continued far into the Christian Era. In Greece, some of the Aegean islands, Sardinia, and Sicily, sick persons are still taken to spend a night in certain churches in the hope of a cure.It was, however, the work of the early philosophers, rather than that of the priests of Asclepius, that impelled Greeks to refuse to be guided solely by supernatural influence and moved them to seek out for themselves the causes and reasons for the strange ways of nature. The 6th-century philosopher Pythagoras, whose chief discovery was the importance of numbers, also investigated the physics of sound, and his views influenced the medical thought of his time. In the 5th century BC Empedocles set forth the view that the universe is composed of four elements—fire, air, earth, and water; this conception led to the doctrine of the four bodily humours (humour): blood; phlegm; choler, or yellow bile; and melancholy, or black bile. The maintenance of health was held to depend upon the harmony of the four humours.Medical thought had reached this stage and had partially discarded the conceptions based upon magic and religion by 460 BC, the year that Hippocrates is said to have been born. Although he has been called the father of medicine, little is known of his life, and there may, in fact, have been several men of this name; or Hippocrates may have been the author of only some, or none, of the books that make up the Hippocratic Collection (Corpus Hippocraticum). Ancient writers held that Hippocrates taught and practiced medicine in Cos, the island of his birth, and in other parts of Greece, including Athens, and that he died at an advanced age.Whether Hippocrates was one man or several, the works attributed to him mark the stage in Western medicine where disease was coming to be regarded as a natural rather than a supernatural phenomenon and doctors were encouraged to look for physical causes of illness. Some of the works, notably the Aphorismi (Aphorisms), were used as textbooks until the 19th century. The first and best-known aphorism is, “Life is Short, Art long, Occasion sudden and dangerous, Experience deceitful, and Judgment difficult” (often shortened to the Latin tag, “Ars longa, vita brevis”). This is followed by brief comments on diseases and symptoms, many of which remain valid.The thermometer and the stethoscope were not then known; nor, indeed, did Hippocrates employ any aid to diagnosis beyond his own powers of observation and logical reasoning. He had an extraordinary ability to foretell the course of a malady, and he laid more stress upon the expected outcome, or prognosis, of a disease than upon its identification, or diagnosis. He had no patience with the idea that disease was a punishment sent by the gods. Writing of epilepsy, then called “the sacred disease,” he said, “It is not any more sacred than other diseases, but has a natural cause, and its supposed divine origin is due to man's inexperience. Every disease,” he continued, “has its own nature, and arises from external causes.”Hippocrates noted the effect of food, of occupation, and especially of climate in causing disease, and one of his most interesting books, entitled De aëre, aquis et locis (Air, Waters and Places), would today be classed as a treatise on human ecology. Pursuing this line of thought, Hippocrates stated that “our natures are the physicians of our diseases” and advocated that this tendency to natural cure should be fostered. He laid much stress on diet and the use of few drugs. He knew well how to describe illness clearly and concisely and recorded failures as well as successes; he viewed disease with the eye of the naturalist and studied the entire patient in his environment.Perhaps the greatest legacy of Hippocrates is the charter of medical conduct embodied in the so-called Hippocratic oath, which has been adopted as a pattern by physicians throughout the ages:I swear by Apollo the physician, and Asclepius, and Health, and All-heal, and all the gods and goddesses . . . to reckon him who taught me this Art equally dear to me as my parents, to share my substance with him, and relieve his necessities if required; to look upon his offspring in the same footing as my own brothers, and to teach them this art, if they shall wish to learn it, without fee or stipulation; and that by precept, lecture, and every other mode of instruction, I will impart a knowledge of the Art to my own sons, and those of my teachers, and to disciples bound by a stipulation and oath according to the law of medicine, but to none others. I will follow that system of regimen which, according to my ability and judgment, I consider for the benefit of my patients, and abstain from whatever is deleterious and mischievous. I will give no deadly medicine to any one if asked, nor suggest any such counsel; and in like manner I will not give to a woman a pessary to produce abortion. . . . Into whatever houses I enter, I will go into them for the benefit of the sick, and will abstain from every voluntary act of mischief and corruption; and, further from the seduction of females or males, of freemen and slaves. Whatever, in connection with my professional practice or not, in connection with it, I see or hear, in the life of men, which ought not to be spoken of abroad, I will not divulge, as reckoning that all such should be kept secret.Not strictly an oath, it was, rather, an ethical code or ideal, an appeal for right conduct. In one or other of its many versions, it has guided the practice of medicine throughout the world for more than 2,000 years.In the following century the work of Aristotle, regarded as the first great biologist, was of inestimable value to medicine. A pupil of Plato at Athens and tutor to Alexander the Great, Aristotle studied the entire world of living things. He laid what can be identified as the foundations of comparative anatomy and embryology, and his views influenced scientific thinking for the next 2,000 years.After the time of Aristotle, the centre of Greek culture shifted to Alexandria, where a famous medical school was established in about 300 BC. There, the two best medical teachers were Herophilus, whose treatise on anatomy may have been the first of its kind, and Erasistratus (Erasistratus Of Ceos), regarded by some as the founder of physiology. Erasistratus noted the difference between sensory and motor nerves but thought that the nerves were hollow tubes containing fluid and that air entered the lungs and heart and was carried through the body in the arteries. Alexandria continued as a centre of medical teaching even after the Roman Empire had attained supremacy over the Greek world, and medical knowledge remained predominantly Greek.Asclepiades Of Bithynia (born 124 BC) differed from Hippocrates in that he denied the healing power of nature and insisted that disease should be treated safely, speedily, and agreeably. An opponent of the humoral theory, he drew upon the atomic theory of the 5th-century Greek philosopher Democritus in advocating a doctrine of strictum et laxum—the attribution of disease to the contracted or relaxed condition of the solid particles that he believed make up the body. To restore harmony among the particles and thus effect cures, Asclepiades used typically Greek remedies: massage, poultices, occasional tonics, fresh air, and corrective diet. He gave particular attention to mental (mental hygiene) disease, clearly distinguishing hallucinations from delusions. He released the insane from confinement in dark cellars and prescribed a regimen of occupational therapy, soothing music, soporifics (especially wine), and exercises to improve the attention and memory.Asclepiades did much to win acceptance for Greek medicine in Rome. Aulus Cornelius Celsus (Celsus, Aulus Cornelius), the Roman nobleman who wrote De medicina about AD 30, gave a classic account of Greek medicine of the time, including descriptions of elaborate surgical operations. His book, overlooked in his day, enjoyed a wide reputation during the Renaissance.During the early centuries of the Christian Era, Greek doctors thronged to Rome (ancient Rome). The most illustrious of them was Galen (Galen Of Pergamum), who began practicing there in AD 161. He acknowledged his debt to Hippocrates and followed the Hippocratic method, accepting the doctrine of the humours. He laid stress on the value of anatomy, and he virtually founded experimental physiology. Galen recognized that the arteries contain blood and not merely air. He showed how the heart sets the blood in motion in an ebb and flow fashion, but he had no idea that the blood circulates. Dissection of the human body was at that time illegal, so that he was forced to base his knowledge upon the examination of animals, particularly apes. A voluminous writer who stated his views forcibly and with confidence, he remained for centuries the undisputed authority from whom no one dared to differ.Another influential physician of the 2nd century AD was Soranus of Ephesus, who wrote authoritatively on childbirth, infant care, and women's diseases. An opponent of abortion, he advocated numerous means of contraception. He also described how to assist a difficult delivery by turning the fetus in the uterus (podalic version), a life-saving technique that was subsequently lost sight of until it was revived in the 16th century.Although the contribution of Rome to the practice of medicine was negligible compared with that of Greece, in matters of public health the Romans set the world a great example. The city of Rome had an unrivaled water supply. Gymnasiums and public baths were provided, and there was even domestic sanitation and adequate disposal of sewage. The army had its medical officers, public physicians were appointed to attend the poor, and hospitals were built; a Roman hospital excavated near Düsseldorf, Ger., was found to be strikingly modern in design.Christian and Muslim reservoirs of learningAfter the fall of Rome, learning was no longer held in high esteem, experiment was discouraged, and originality became a dangerous asset. During the early Middle Ages medicine passed into the widely diverse hands of the Christian Church and Arab scholars.Translators and saintsIt is sometimes stated that the early Christian (Christianity) Church had an adverse effect upon medical progress. Disease was regarded as a punishment for sin, and such chastening demanded only prayer and repentance. Moreover, the human body was held sacred and dissection was forbidden. But the infinite care and nursing bestowed upon the sick under Christian auspices must outweigh any intolerance shown toward medicine in the early days.Perhaps the greatest service rendered to medicine by the church was the preservation and transcription of the classical Greek medical manuscripts. These were translated into Latin in many medieval monasteries, and the Nestorian Christians (an Eastern church) established a school of translators to render the Greek texts into Arabic. This famous school, and also a great hospital, were located at Jundi Shāhpūr in southwest Persia, where the chief physician was Jurjīs ibn Bukhtīshūʿ, the first of a dynasty of translators and physicians that lasted for six generations. A later translator of great renown was Ḥunayn ibn Isḥāq, or Johannitus (born AD 809), whose translations were said to be worth their weight in gold.About this time there appeared a number of saints (saint) whose names were associated with miraculous cures. Among the earliest of these were twin brothers, Cosmas and Damian, who suffered martyrdom (c. AD 303) and who became the patron saints (patron saint) of medicine. Other saints were invoked as powerful healers of certain diseases, such as St. Vitus for chorea (or St. Vitus' dance) and St. Anthony for erysipelas (or St. Anthony's fire). The cult of these saints was widespread in medieval times, and a later cult, that of St. Roch for plague, was widespread during the plague-ridden years of the 14th century.Arabian medicineA second reservoir of medical learning during those times was the great Muslim empire (Caliphate), which extended from Persia to Spain. Although it is customary to speak of Arabian medicine in describing this period, not all of the physicians were Arabs or natives of Arabia. Nor, indeed, were they all Muslims (Islāmic world): some were Jews, some Christians, and they were drawn from all parts of the empire. One of the earliest figures was Rhazes (Rāzī, ar-), a Persian (Iran) born in the last half of the 9th century near modern Tehrān, who wrote a voluminous treatise on medicine, Kitāb al-hāḳī (“Comprehensive Book”), but whose most famous work, De variolis et morbillis (A Treatise on the Smallpox and Measles), distinguishes between these two diseases and gives a clear description of both.Of later date was Avicenna (980–1037), also a Persian, who has been called the prince of physicians and whose tomb at Hamadan has become a place of pilgrimage. He could repeat the Qurʾān before he was 10 years old and at the age of 18 became court physician. His principal medical work, al-Qānūn fī aṭ-ṭibb (The Canon of Medicine), became a classic and was used at many medical schools—at Montpellier, Fr., as late as 1650—and reputedly is still used in the East.The greatest contribution of Arabian medicine was in chemistry and in the knowledge and preparation of medicines. The chemists of that time were alchemists, and their pursuit was mainly a search for the philosopher's stone, which supposedly would turn common metals into gold. In the course of their experiments, however, numerous substances were named and characterized, and some were found to have medicinal value. Many drugs now in use are of Arab origin, as are such processes as distillation and sublimation.At that period, and indeed throughout most historical times, surgery was considered inferior to medicine, and surgeons were held in low regard. The renowned Spanish surgeon Abū al-Qāsim (Albucasis), however, did much to raise the status of surgery in Córdoba, an important centre of commerce and culture with a hospital and medical school equal to those of Cairo and Baghdad. A careful and conservative practitioner, he wrote the first illustrated surgical text, which held wide influence in Europe for centuries.Another great doctor of Córdoba, born in the 12th century, just as the sun of Arabian culture was setting, was the Jewish philosopher Maimonides (Maimonides, Moses). Banished from the city because he would not become a Muslim, he eventually went to Cairo, where the law was more lenient and where he acquired a reputation so high that he became physician to Saladin, the Saracen leader. (He was the original of El Hakim in Sir Walter Scott's Talisman.) A few of his works, written in Hebrew, were eventually translated into Latin and printed.Medieval and Renaissance EuropeAt about the same time that Arabian medicine flourished, the first organized medical school in Europe was established at Salerno, in southern Italy. Although the school of Salerno produced no brilliant genius and no startling discovery, it was the outstanding medical institution of its time and the parent of the great medieval schools soon to be founded at Montpellier and Paris, in France, and at Bologna and Padua, in Italy. Salerno drew scholars from near and far. Remarkably liberal in some of its views, Salerno admitted women as medical students. The school owed much to the enlightened Holy Roman emperor Frederick II, who decreed in 1221 that no one should practice medicine until he had been publicly approved by the masters of Salerno.The Salernitan school also produced a literature of its own; the best-known work, of uncertain date and of composite authorship, was the Regimen Sanitatis Salernitanum (“Salernitan Guide to Health”). Written in verse, it has appeared in numerous editions and has been translated into many languages. Among its oft-quoted couplets is the following:Use three physicians still, first Doctor Quiet,Next Doctor Merryman, and Doctor Diet.Salerno yielded its place as the premier medical school of Europe to Montpellier in about 1200. John of Gaddesden, the model for the “doctour of physick” in Chaucer's Canterbury Tales, was one of the English students there. That he relied upon astrology and upon the doctrine of the humours is evident from Chaucer's description:Well could he guess the ascending of the starWherein his patient's fortunes settled were.He knew the course of every malady,Were it of cold or heat or moist or dry.Medieval physicians analyzed symptoms, examined excreta, and made their diagnoses. Then they might prescribe diet, rest, sleep, exercise, or baths; or they could administer emetics and purgatives or bleed the patient. Surgeons could treat fractures and dislocations, repair hernias, and perform amputations and a few other operations. Some of them prescribed opium, mandragora, or alcohol to deaden pain. Childbirth was left to midwives, who relied on folklore and tradition.Great hospitals were established during the Middle Ages by religious foundations, and infirmaries were attached to abbeys, monasteries, priories, and convents. Doctors and nurses in these institutions were members of religious orders and combined spiritual with physical healing.The spread of new learningAmong the teachers of medicine in the medieval universities there were many who clung to the past, but there were not a few who determined to explore new lines of thought. The new learning of the Renaissance, born in Italy, grew and expanded slowly. Two great 13th-century scholars who influenced medicine were Roger Bacon, an active observer and tireless experimenter, and Albertus Magnus, a distinguished philosopher and scientific writer.About this time Mondino dei Liucci (Mondino De' Luzzi) taught at Bologna. Prohibitions against human dissection were slowly lifting, and Mondino performed his own dissections rather than following the customary procedure of entrusting the task to a menial. Although he perpetuated the errors of Galen, his Anothomia, published in 1316, was the first practical manual of anatomy. Foremost among the surgeons of the day was Guy de Chauliac (Chauliac, Guy de), a physician to three popes at Avignon. His Chirurgia magna (“Great Surgery”), based on observation and experience, had a profound influence upon the progress of surgery.The Renaissance in the 14th, 15th, and 16th centuries was much more than just a reviving of interest in Greek and Roman culture; it was rather a change of outlook, an eagerness for discovery, a desire to escape from the limitations of tradition and to explore new fields of thought and action. In medicine, it was perhaps natural that anatomy and physiology, the knowledge of the human body and its workings, should be the first aspects of medical learning to receive attention from those who realized the need for reform.It was in 1543 that Andreas Vesalius (Vesalius, Andreas), a young Belgian professor of anatomy at the University of Padua, published De humani corporis fabrica (“On the Structure of the Human Body”). Based on his own dissections, this seminal work corrected many of Galen's errors. By his scientific observations and methods, Vesalius showed that Galen could no longer be regarded as the final authority. His work at Padua was continued by Gabriel Fallopius and, later, by Hieronymus Fabricius ab Aquapendente (Fabricius ab Aquapendente, Hieronymus); it was his work on the valves in the veins, De venarum ostiolis (1603), that suggested to his pupil William Harvey his revolutionary theory of the circulation of the blood, one of the great medical discoveries.Surgery profited from the new outlook in anatomy, and the great reformer Ambroise Paré (Paré, Ambroise) dominated the field in the 16th century. Paré was surgeon to four kings of France, and he has deservedly been called the father of modern surgery. In his autobiography, written after he had retired from 30 years of service as an army surgeon, Paré described how he had abolished the painful practice of cautery to stop bleeding and used ligatures and dressings instead. His favourite expression, “I dressed him; God healed him,” is characteristic of this humane and careful doctor.In Britain during this period surgery, which was performed by barber-surgeons, was becoming regulated and organized under royal charters. Companies were thus formed that eventually became the royal colleges of surgeons in Scotland and England. Physicians and surgeons united in a joint organization in Glasgow, and a college of physicians was founded in London.The 16th-century medical scene was enlivened by the enigmatic physician and alchemist who called himself Paracelsus. Born in Switzerland, he traveled extensively throughout Europe, gaining medical skills and practicing and teaching as he went. In the tradition of Hippocrates, Paracelsus stressed the power of nature to heal; but unlike Hippocrates he believed also in the power of supernatural forces, and he violently attacked the medical treatments of his day. Eager for reform, he allowed his intolerance to outweigh his discretion, as when he prefaced his lectures at Basel by publicly burning the works of Avicenna and Galen. The authorities and medical men were understandably outraged. Widely famous in his time, Paracelsus remains a controversial figure to this day. Despite his turbulent career, however, he did attempt to bring a more rational approach to diagnosis and treatment, and he introduced the use of chemical drugs in place of herbal remedies.A contemporary of Paracelsus, Girolamo Fracastoro (Fracastoro, Girolamo) of Italy was a scholar cast from a very different mold. His account of the disease syphilis, entitled Syphilis sive morbus Gallicus (1530; “Syphilis or the French Disease”), was written in verse. Although Fracastoro called syphilis the French disease, others called it the Neapolitan disease, for it was said to have been brought to Naples from America by the sailors of Christopher Columbus. Its origin is still questioned, however. Fracastoro was interested in epidemic infection, and he offered the first scientific explanation of disease transmission. In his great work, De contagione et contagiosis morbis (1546), he theorized that the seeds of certain diseases are imperceptible particles transmitted by air or by contact.The EnlightenmentIn the 17th century the natural sciences moved forward on a broad front. There were attempts to grapple with the nature of science, as expressed in the works of thinkers like Francis Bacon, Descartes, and Newton. New knowledge of chemistry superseded the theory that all things are made up of earth, air, fire, and water, and the old Aristotelian ideas began to be discarded. The supreme 17th-century achievement in medicine was Harvey's explanation of the circulation of blood.Harvey and the experimental methodBorn in Folkestone, Eng., William Harvey (Harvey, William) studied at Cambridge University and then spent several years at Padua, where he came under the influence of Fabricius. He established a successful medical practice in London and by precise observation and scrupulous reasoning developed his theory of circulation. In 1628 he published his classic book Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus (Concerning the Motion of the Heart and Blood), often called De Motu Cordis.That the book aroused controversy is not surprising. There were still many who adhered to the teaching of Galen (Galen Of Pergamum) that the blood follows an ebb and flow movement in the blood vessels (human cardiovascular system). Harvey's work was the result of many careful experiments, but few of his critics took the trouble to repeat the experiments, simply arguing in favour of the older view. His second great book, Exercitationes de generatione animalium (“Experiments Concerning Animal Generation”), published in 1651, laid the foundation of modern embryology.Harvey's discovery of the circulation of the blood was a landmark of medical progress; the new experimental method by which the results were secured was as noteworthy as the work itself. Following the method described by the philosopher Francis Bacon, he drew the truth from experience and not from authority.There was one gap in Harvey's argument: he was obliged to assume the existence of the capillary vessels that conveyed the blood from the arteries to the veins. This link in the chain of evidence was supplied by Marcello Malpighi (Malpighi, Marcello) of Bologna (who was born in 1628, the year of publication of De Motu Cordis). With a primitive microscope Malpighi saw a network of tiny blood vessels in the lung of a frog. Harvey also failed to show why the blood circulated. After Robert Boyle had shown that air is essential to animal life, it was Richard Lower who traced the interaction between air and the blood. Eventually the importance of oxygen, which was confused for a time by some as phlogiston, was revealed, although it was not until the late 18th century that the great chemist Antoine-Laurent Lavoisier discovered the essential nature of oxygen and clarified its relation to respiration.Although the compound microscope had been invented slightly earlier, probably in Holland, its development, like that of the telescope, was the work of Galileo. He was the first to insist upon the value of measurement in science and in medicine, thus replacing theory and guesswork with accuracy. The great Dutch microscopist Antonie van Leeuwenhoek (Leeuwenhoek, Antonie van) devoted his long life to microscopical studies and was probably the first to see and describe bacteria, reporting his results to the Royal Society of London. In England, Robert Hooke (Hooke, Robert), who was Boyle's assistant and curator to the Royal Society, published his Micrographia in 1665, which discussed and illustrated the microscopic structure of a variety of materials.The futile search for an easy systemSeveral attempts were made in the 17th century to discover an easy system that would guide the practice of medicine. A substratum of superstition still remained. Richard Wiseman, surgeon to Charles II, affirmed his belief in the “royal touch” as a cure for king's evil, or scrofula, while even the learned English physician Thomas Browne stated that witches really existed. There was, however, a general desire to discard the past and adopt new ideas.The view of the French philosopher René Descartes (Descartes, René) that the human body is a machine and that it functions mechanically had its repercussions in medical thought. One group adopting this explanation called themselves the iatrophysicists; another school, preferring to view life as a series of chemical processes, were called iatrochemists. Santorio Santorio, working at Padua, was an early exponent of the iatrophysical view and a pioneer investigator of metabolism. He was especially concerned with the measurement of what he called “insensible perspiration,” described in his book De statica medicina (1614; “On Medical Measurement”). Another Italian, who developed the idea still further, was Giovanni Alfonso Borelli (Borelli, Giovanni Alfonso), a professor of mathematics at Pisa University, who gave his attention to the mechanics and statics of the body and to the physical laws that govern its movements.The iatrochemical school was founded at Brussels by Jan Baptist van Helmont, whose writings are tinged with the mysticism of the alchemist. A more logical and intelligible view of iatrochemistry was advanced by Franciscus Sylvius, at Leiden; and in England a leading exponent of the same school was Thomas Willis (Willis, Thomas), who is better known for his description of the brain in his Cerebri anatome nervorumque descriptio et usus (“Anatomy of the Brain and Descriptions and Functions of the Nerves”), published in 1664 and illustrated by Christopher Wren.It soon became apparent that no easy road to medical knowledge and practice was to be found along these channels and that the best method was the age-old system of straightforward clinical observation initiated by Hippocrates. The need for a return to these views was strongly urged by Thomas Sydenham (Sydenham, Thomas), well named “the English Hippocrates.” Sydenham was not a voluminous writer and, indeed, had little patience with book learning in medicine; nevertheless he gave excellent descriptions of the phenomena of disease. His greatest service, much needed at the time, was to divert physicians' minds from speculation and lead them back to the bedside, where the true art of medicine could be studied.Medicine in the 18th centuryEven in the 18th century the search for a simple way of healing the sick continued. In Edinburgh the writer and lecturer John Brown (Brown, John) expounded his view that there were only two diseases, sthenic (strong) and asthenic (weak), and two treatments, stimulant and sedative; his chief remedies were alcohol and opium. Lively and heated debates took place between his followers, the Brunonians, and the more orthodox Cullenians (followers of William Cullen (Cullen, William), a professor of medicine at Glasgow), and the controversy spread to the medical centres of Europe.At the opposite end of the scale, at least in regard to dosage, was Samuel Hahnemann (Hahnemann, Samuel), of Leipzig, the originator of homeopathy, a system of treatment involving the administration of minute doses of drugs whose effects resemble the effects of the disease being treated. His ideas had a salutary effect upon medical thought at a time when prescriptions were lengthy and doses were large, and his system has had many followers.By the 18th century the medical school (medical education) at Leiden had grown to rival that of Padua, and many students were attracted there from abroad. Among them was John Monro, an army surgeon, who resolved that his native city of Edinburgh (Edinburgh, University of) should have a similar medical school. He specially educated his son Alexander with a view to having him appointed professor of anatomy, and the bold plan was successful. Alexander Monro (Monro, Alexander, primus) studied at Leiden under Hermann Boerhaave (Boerhaave, Hermann), the central figure of European medicine and the greatest clinical teacher of his time. Subsequently, three generations of Alexander Monros taught anatomy at Edinburgh University over a continuous period of 126 years. Medical education was increasingly incorporated into the universities of Europe, and Edinburgh became the leading academic centre for medicine in Britain.In 18th-century London, Scottish doctors were the leaders in surgery and obstetrics (obstetrics and gynecology). The noted teacher John Hunter (Hunter, John) conducted extensive researches in comparative anatomy and physiology, founded surgical pathology, and raised surgery to the level of a respectable branch of science. His brother William Hunter (Hunter, William), an eminent teacher of anatomy, became famous as an obstetrician. Male doctors were now attending women in childbirth, and the leading obstetrician in London was William Smellie (Smellie, William). His well-known Treatise on the Theory and Practice of Midwifery, published in three volumes in 1752–64, contained the first systematic discussion on the safe use of obstetrical forceps, which have since saved countless lives. Smellie placed midwifery on a sound scientific footing and helped to establish obstetrics as a recognized medical discipline.The science of modern pathology also had its beginnings in this century. Giovanni Battista Morgagni (Morgagni, Giovanni Battista), of Padua, in 1761 published his massive work De sedibus et causis morborum (The Seats and Causes of Diseases Investigated by Anatomy), a description of the appearances found by postmortem examination of almost 700 cases, in which he attempted to correlate the findings after death with the clinical picture in life.On the basis of work begun in the 18th century, René Laënnec (Laënnec, René-Théophile-Hyacinthe), a native of Brittany, who practiced medicine in Paris, invented a simple stethoscope, or cylindre, as it was originally called. In 1819 he wrote a treatise, De l'auscultation médiate (“On Mediate auscultation”), describing many of the curious sounds in the heart and lungs that are revealed by the instrument. Meanwhile a Viennese physician, Leopold Auenbrugger (Auenbrugger von Auenbrugg, Leopold), discovered another method of investigating diseases of the chest, that of percussion. The son of an innkeeper, he is said to have conceived the idea of tapping with the fingers when he recalled that he had used this method to gauge the level of the fluid contents of his father's casks.One highly significant medical advance, late in the century, was vaccination (vaccine). smallpox, disfiguring and often fatal, was widely prevalent. inoculation, which had been practiced in the East, was popularized in England in 1721–22 by Lady Mary Wortley Montagu (Montagu, Lady Mary Wortley), who is best known for her letters. She observed the practice in Turkey, where it produced a mild form of the disease, thus securing immunity, although not without danger. The next step was taken by Edward Jenner (Jenner, Edward), a country practitioner who had been a pupil of John Hunter. In 1796 Jenner began inoculations with material from cowpox (the bovine form of the disease); and when he later inoculated the same subject with smallpox, the disease did not appear. This procedure—vaccination—has been responsible for eradicating the disease.public health and hygiene were receiving more attention during the 18th century. Population statistics began to be kept, and suggestions arose concerning health legislation. Hospitals were established for a variety of purposes. In Paris, Philippe Pinel (Pinel, Philippe) initiated bold reforms in the care of the mentally ill, releasing them from their chains and discarding the long-held notion that insanity was caused by demon possession.Conditions improved for sailors and soldiers as well. James Lind (Lind, James), a British naval surgeon from Edinburgh, recommended fresh fruits and citrus juices to prevent scurvy, a remedy discovered by the Dutch in the 16th century. When the British navy adopted Lind's advice—decades later—this deficiency disease was eliminated. In 1752 a Scotsman, John Pringle (Pringle, Sir John, 1st Baronet), published his classic Observations on the Diseases of the Army, which contained numerous recommendations for the health and comfort of the troops. Serving with the British forces during the War of the Austrian Succession, he suggested in 1743 that military hospitals on both sides should be regarded as sanctuaries; this plan eventually led to the establishment of the Red Cross (Red Cross and Red Crescent) organization in 1864.Two pseudoscientific doctrines relating to medicine emerged from Vienna in the latter part of the century and attained wide notoriety. Mesmerism, a belief in “animal magnetism” sponsored by Franz Anton Mesmer, probably owed any therapeutic value it had to suggestions given while the patient was under hypnosis. phrenology, propounded by Franz Joseph Gall, held that the contours of the skull were a guide to an individual's mental faculties and character traits; this theory remained popular throughout the 19th century.At the same time, sound scientific thinking was making steady progress, and advances in physics, chemistry, and the biological sciences were converging to form a rational scientific basis for every branch of clinical medicine. New knowledge disseminated thoughout Europe and traveled across the sea, where centres of medical excellence were being established in America.The rise of scientific medicine in the 19th centuryThe portrayal of the history of medicine becomes more difficult in the 19th century. Discoveries multiply, and the number of eminent doctors is so great that the history is apt to become a series of biographies. Nevertheless, it is possible to discern the leading trends in modern medical thought.PhysiologyBy the beginning of the 19th century, the structure of the human body was almost fully known, due to new methods of microscopy and of injections. Even the body's microscopic structure was understood. But as important as anatomical knowledge was an understanding of physiological (physiology) processes, which were rapidly being elucidated, especially in Germany. There, physiology became established as a distinct science under the guidance of Johannes Müller (Müller, Johannes Peter), who was a professor at Bonn and then at the University of Berlin. An energetic worker and an inspiring teacher, he described his discoveries in a famous textbook, Handbuch der Physiologie des Menschen (“Manual of Human Physiology”), published in the 1830s.Among Müller's illustrious pupils were Hermann von Helmholtz (Helmholtz, Hermann von), who made significant discoveries relating to sight and hearing and who invented the ophthalmoscope; and Rudolf Virchow (Virchow, Rudolf), one of the century's great medical scientists, whose outstanding achievement was his conception of the cell as the centre of all pathological changes. Virchow's work Die Cellularpathologie, published in 1858, gave the deathblow to the outmoded view that disease is due to an imbalance of the four humours.In France the most brilliant physiologist of the time was Claude Bernard (Bernard, Claude), whose many important discoveries were the outcome of carefully planned experiments. His researches clarified the role of the pancreas in digestion, revealed the presence of glycogen in the liver, and explained how the contraction and expansion of the blood vessels are controlled by vasomotor nerves. He proposed the concept of the internal environment—the chemical balance in and around the cells—and the importance of its stability. His Introduction à l'étude de la médecine expérimentale (1865; An Introduction to the Study of Experimental Medicine) is still worthy of study by all who undertake research.Verification of the germ theoryPerhaps the overarching medical advance of the 19th century, certainly the most spectacular, was the conclusive demonstration that certain diseases, as well as the infection of surgical wounds, were directly caused by minute living organisms. This discovery changed the whole face of pathology and effected a complete revolution in the practice of surgery.The idea that disease was caused by entry into the body of imperceptible particles was of ancient date. It had been expressed by the Roman encyclopaedist Varro (Varro, Marcus Terentius) as early as 100 BC, by Fracastoro in 1546, by Athanasius Kircher and Pierre Borel about a century later, and by Francesco Redi (Redi, Francesco), who in 1684 wrote his Osservazioni intorno agli animali viventi che si trovano negli animali viventi (“Observations on Living Animals Which Are to Be Found Within Other Living Animals”), in which he sought to disprove the idea of spontaneous generation. Everything must have a parent, he wrote; only life produces life. A 19th-century pioneer in this field, regarded by some as founder of the parasitic theory of infection, was Agostino Bassi (Bassi, Agostino) of Italy, who showed that a disease of silkworms was caused by a fungus that could be destroyed by chemical agents.The main credit for establishing the science of bacteriology must be accorded to the French chemist Louis Pasteur (Pasteur, Louis). It was Pasteur who, by a brilliant series of experiments, proved that the fermentation of wine and the souring of milk are caused by living microorganisms. His work led to the pasteurization of milk and solved problems of agriculture and industry as well as those of animal and human diseases. He successfully employed inoculations to prevent anthrax in sheep and cattle, chicken cholera in fowl, and finally rabies in humans and dogs. The latter resulted in the widespread establishment of Pasteur institutes.From Pasteur, Joseph Lister (Lister, Joseph, Baron Lister, Of Lyme Regis) derived the concepts that enabled him to introduce the antiseptic principle into surgery. In 1865 Lister, a professor of surgery at Glasgow University, began placing an antiseptic barrier of carbolic acid between the wound and the germ-containing atmosphere. Infections and deaths fell dramatically, and his pioneering work led to more refined techniques of sterilizing the surgical environment.Obstetrics had already been robbed of some of its terrors by Alexander Gordon at Aberdeen, Scot., Oliver Wendell Holmes (Holmes, Oliver Wendell) at Boston, and Ignaz Semmelweis (Semmelweis, Ignaz Philipp) at Vienna and Pest (Budapest), who advocated disinfection of the hands and clothing of midwives and medical students who attended confinements. These measures produced a marked reduction in cases of puerperal fever, the bacterial (bacteria) scourge of women following childbirth.Another pioneer in bacteriology was the German physician Robert Koch (Koch, Robert), who showed how bacteria could be cultivated, isolated, and examined in the laboratory. A meticulous investigator, Koch discovered the organisms of tuberculosis, in 1882, and cholera, in 1883. By the end of the century many other disease-producing microorganisms had been identified.Discoveries in clinical medicine and anesthesiaThere was perhaps some danger that in the search for bacteria other causes of disease would escape detection. Many physicians, however, were working along different lines in the 19th century. Among them were a group attached to Guy's Hospital, in London: Richard Bright, Thomas Addison, and Sir William Gull. Bright contributed significantly to the knowledge of kidney diseases, including Bright's disease, and Addison gave his name to disorders of the adrenal glands and the blood. Gull, a famous clinical teacher, left a legacy of pithy aphorisms that might well rank with those of Hippocrates.In Dublin Robert Graves and William Stokes introduced new methods in clinical diagnosis and medical training; while in Paris a leading clinician, Pierre-Charles-Alexandre Louis, was attracting many students from America by the excellence of his teaching. By the early 19th century the United States was ready to send back the results of its own researches and breakthroughs. In 1809, in a small Kentucky town, Ephraim McDowell boldly operated on a woman—without anesthesia or antisepsis—and successfully removed a large ovarian tumour. William Beaumont (Beaumont, William), in treating a shotgun wound of the stomach, was led to make many original observations that were published in 1833 as Experiments and Observations on the Gastric Juice and the Physiology of Digestion.The most famous contribution by the United States to medical progress at this period was undoubtedly the introduction of general anesthesia (anesthetic), a procedure that not only liberated the patient from the fearful pain of surgery but also enabled the surgeon to perform more extensive operations. The discovery was marred by controversy. Crawford Long, Gardner Colton, Horace Wells, and Charles Jackson are all claimants for priority; some used nitrous oxide gas, and others employed ether (ethyl ether), which was less capricious. There is little doubt, however, that it was William Thomas Morton (Morton, William Thomas Green) who, on Oct. 16, 1846, at Massachusetts General Hospital, in Boston, first demonstrated before a gathering of physicians the use of ether as a general anesthetic. The news quickly reached Europe, and general anesthesia soon became prevalent in surgery. At Edinburgh, the professor of midwifery, James Young Simpson (Simpson, Sir James Young, 1st Baronet), had been experimenting upon himself and his assistants, inhaling various vapours with the object of discovering an effective anesthetic. In November 1847 chloroform was tried with complete success, and soon it was preferred to ether and became the anesthetic of choice.Advances at the end of the centuryWhile antisepsis and anesthesia placed surgery on an entirely new footing, similarly important work was carried out in other fields of study, such as parasitology and disease transmission. Patrick Manson (Manson, Sir Patrick), a British pioneer in tropical medicine, showed in China, in 1877, how insects can carry disease and how the embryos of the Filaria (filarial worm) worm, which can cause elephantiasis, are transmitted by the mosquito. Manson explained his views to a British army surgeon, Ronald Ross (Ross, Sir Ronald), then working on the problem of malaria, and Ross discovered the malarial parasite in the stomach of the Anopheles mosquito in 1897.In Cuba, Carlos Finlay (Finlay, Carlos J.) expressed the view, in 1881, that yellow fever is carried by the Stegomyia mosquito. Following his lead, the Americans Walter Reed, William Gorgas, and others were able to conquer the scourge of yellow fever in Panama and made possible the completion of the Panama Canal by reducing the death rate there from 176 per 1,000 to 6 per 1,000.Other victories in preventive medicine ensued, because the maintenance of health was now becoming as important a concern as the cure of disease; and the 20th century was to witness the evolution and progress of national health services in a number of countries. In addition, spectacular advances in diagnosis and treatment followed the discovery of X rays by Wilhelm Conrad Röntgen, in 1895, and of radium by Pierre and Marie Curie in 1898. Before the turn of the century, too, the vast new field of psychiatry had been opened up by Sigmund Freud. The tremendous increase in scientific knowledge during the 19th century radically altered and expanded the practice of medicine. Concern for upholding the quality of services led to the establishment of public and professional bodies to govern the standards for medical training and practice.Douglas James Guthrie Philip RhodesMedicine in the 20th centuryThe 20th century has produced such a plethora of discoveries and advances that in some ways the face of medicine has changed out of all recognition. In 1901, for instance, in the United Kingdom the expectation of life at birth, a primary indicator of the effect of health care on mortality (but also reflecting the state of health education, housing, and nutrition), was 48 years for males and 51.6 years for females. After steady increases, by the 1980s life expectancy had reached 71.4 years for males and 77.2 years for females. Other industrialized nations showed similar dramatic increases. Indeed, the outlook has so altered that, with the exception of diseases such as cancer and AIDS, attention has become focused on morbidity rather than mortality, and the emphasis has changed from keeping people alive to keeping them fit.The rapid progress of medicine in this era was reinforced by enormous improvements in communication between scientists throughout the world. Through publications, conferences, and—later—computers and electronic media, they freely exchanged ideas and reported on their endeavours. No longer was it common for an individual to work in isolation. Although specialization increased, teamwork became the norm. It consequently has become more difficult to ascribe medical accomplishments to particular individuals.In the first half of the century, emphasis continued to be placed on combating infection, and notable landmarks were also attained in endocrinology, nutrition, and other areas. In the years following World War II, insights derived from cell biology altered basic concepts of the disease process; new discoveries in biochemistry and physiology opened the way for more precise diagnostic tests and more effective therapies; and spectacular advances in biomedical engineering enabled the physician and surgeon to probe into the structures and functions of the body by noninvasive imaging techniques like ultrasound (sonar), computerized axial tomography (CAT), and nuclear magnetic resonance (NMR). With each new scientific development, medical practices of just a few years earlier became obsolete.Infectious diseases and chemotherapyIn the years following the turn of the century, ongoing research concentrated on the nature of infectious diseases and their means of transmission. Increasing numbers of pathogenic organisms were discovered and classified. Some, such as the rickettsias, which cause diseases like typhus, were smaller than bacteria; some were larger, such as the protozoans that engender malaria and other tropical diseases. The smallest to be identified were the viruses, producers of many diseases, among them mumps, measles, German measles, and poliomyelitis; and in 1910 Peyton Rous showed that a virus could also cause a malignant tumour, a sarcoma in chickens.There was still little to be done for the victims of most infectious organisms beyond drainage, poultices, and ointments, in the case of local infections, and rest and nourishment for severe diseases. The search for treatments aimed at both vaccines and chemical remedies.Ehrlich and arsphenamineGermany was well to the forefront in medical progress. The scientific approach to medicine had been developed there long before it spread to other countries, and postgraduates flocked to German medical schools from all over the world. The opening decade of the 20th century has been well described as the golden age of German medicine. Outstanding among its leaders was Paul Ehrlich (Ehrlich, Paul).While still a student, Ehrlich carried out some work on lead poisoning from which he evolved the theory that was to guide much of his subsequent work—that certain tissues have a selective affinity for certain chemicals. He experimented with the effects of various chemical substances on disease organisms. In 1910, with his colleague Sahachiro Hata, he conducted tests on arsphenamine, once sold under the commercial name Salvarsan. Their success inaugurated the chemotherapeutic (chemotherapy) era, which was to revolutionize the treatment and control of infectious diseases. Salvarsan, a synthetic preparation containing arsenic, is lethal to the microorganism responsible for syphilis. Until the introduction of penicillin, Salvarsan or one of its modifications remained the standard treatment of syphilis and went far toward bringing this social and medical scourge under control.sulfonamide drugsIn 1932 the German bacteriologist Gerhard Domagk (Domagk, Gerhard) announced that the red dye Prontosil is active against streptococcal infections in mice and humans. Soon afterward French workers showed that its active antibacterial agent is sulfanilamide. In 1936 the English physician Leonard Colebrook and his colleagues provided overwhelming evidence of the efficacy of both Prontosil and sulfanilamide in streptococcal septicemia (bloodstream infection), thereby ushering in the sulfonamide era. New sulfonamides, which appeared with astonishing rapidity, had greater potency, wider antibacterial range, or lower toxicity. Some stood the test of time; others, like the original sulfanilamide and its immediate successor, sulfapyridine, were replaced by safer and more powerful successors.A dramatic episode in medical history occurred in 1928, when Alexander Fleming (Fleming, Sir Alexander) noticed the inhibitory action of a stray mold on a plate culture of staphylococcus bacteria in his laboratory at St. Mary's Hospital, London. Many other bacteriologists must have made the observation, but none had realized the possible implications. The mold was a strain of Penicillium—P. notatum—which gave its name to the now-famous drug penicillin. In spite of his conviction that penicillin was a potent antibacterial agent, Fleming was unable to carry his work to fruition, mainly because biochemists at the time were unable to isolate it in sufficient quantities or in a sufficiently pure form to allow its use on patients.Ten years later Howard Florey, Ernst Chain, and their colleagues at Oxford University took up the problem again They isolated penicillin in a form that was fairly pure (by standards then current) and demonstrated its potency and relative lack of toxicity. By then World War II had begun, and techniques to facilitate commercial production were developed in the United States. By 1944 adequate amounts were available to meet the extraordinary needs of wartime.Antituberculous drugsWhile penicillin is the most useful and the safest antibiotic, it suffers from certain disadvantages. The most important of these is that it is not active against Mycobacterium tuberculosis, the bacillus of tuberculosis. In view of the importance of tuberculosis as a public health hazard, this is a serious defect. The position was rapidly rectified when, in 1944, Selman Waksman (Waksman, Selman Abraham), Albert Schatz, and Elizabeth Bugie announced the discovery of streptomycin from cultures of a soil organism, Streptomyces griseus, and stated that it was active against M. tuberculosis. Subsequent clinical trials amply confirmed this claim. Streptomycin suffers, however, from the great disadvantage that the tubercle bacillus tends to become resistant to it. Fortunately, other drugs became available to supplement it, the two most important being para-aminosalicylic acid (PAS) and isoniazid. With a combination of two or more of these preparations, the outlook in tuberculosis improved immeasurably. The disease was not conquered, but it was brought well under control.Other antibioticsPenicillin is not effective over the entire field of microorganisms pathogenic to humans. During the 1950s the search for antibiotics to fill this gap resulted in a steady stream of them, some with a much wider antibacterial range than penicillin (the so-called broad-spectrum antibiotics) and some capable of coping with those microorganisms that are inherently resistant to penicillin or that have developed resistance through exposure to penicillin.This tendency of microorganisms to develop resistance to penicillin at one time threatened to become almost as serious a problem as the development of resistance to streptomycin by the bacillus of tuberculosis. Fortunately, early appreciation of the problem by clinicians resulted in more discriminate use of penicillin. Scientists continued to look for means of obtaining new varieties of penicillin, and their researches produced the so-called semisynthetic antibiotics, some of which are active when taken by mouth, while others are effective against microorganisms that have developed resistance to the earlier form of penicillin.Dramatic though they undoubtedly were, the advances in chemotherapy still left one important area vulnerable, that of the viruses (virus). It was in bringing viruses under control that advances in immunology—the study of immunity—played such a striking part. One of the paradoxes of medicine is that the first large-scale immunization against a viral (virology) disease was instituted and established long before viruses were discovered. When Edward Jenner introduced vaccination against the virus that causes smallpox, the identification of viruses was still 100 years in the future. It took almost another half century to discover an effective method of producing antiviral vaccines that were both safe and effective.In the meantime, however, the process by which the body reacts against infectious organisms to generate immunity became better understood. In Paris, Élie Metchnikoff had already detected the role of white blood cells in the immune reaction, and Jules Bordet had identified antibodies in the blood serum. The mechanisms of antibody activity were used to devise diagnostic tests for a number of diseases. In 1906 August von Wassermann (Wassermann, August von) gave his name to the blood test for syphilis, and in 1908 the tuberculin test—the skin test for tuberculosis—came into use. At the same time, methods of producing effective substances for inoculation were improved, and immunization against bacterial diseases made rapid progress.Antibacterial vaccinationIn 1897 the English bacteriologist Almroth Wright (Wright, Sir Almroth Edward) introduced a vaccine prepared from killed typhoid bacilli as a preventive of typhoid. Preliminary trials in the Indian army produced excellent results, and typhoid vaccination was adopted for the use of British troops serving in the South African War. Unfortunately, the method of administration was inadequately controlled, and the government sanctioned inoculations only for soldiers that “voluntarily presented themselves for this purpose prior to their embarkation for the seat of war.” The result was that, according to the official records, only 14,626 men volunteered out of a total strength of 328,244 who served during the three years of the war. Although later analysis showed that inoculation had had a beneficial effect, there were 57,684 cases of typhoid—approximately one in six of the British troops engaged—with 9,022 deaths.A bitter controversy over the merits of the vaccine followed, but before the outbreak of World War I immunization had been officially adopted by the army. Comparative statistics would seem to provide striking confirmation of the value of antityphoid inoculation, even allowing for the better sanitary arrangements in the latter war. In the South African War the annual incidence of enteric infections (typhoid and paratyphoid) was 105 per 1,000 troops, and the annual death rate was 14.6 per 1,000; the comparable figures for World War I were 2.35 and 0.139, respectively.It is perhaps a sign of the increasingly critical outlook that developed in medicine in the post-1945 era that experts continued to differ on some aspects of typhoid immunization. There was no question as to its fundamental efficacy, but there was considerable variation of opinion as to the best vaccine to use and the most effective way of administering it. Moreover, it was often difficult to decide to what extent the decline in typhoid was attributable to improved sanitary conditions and what to the greater use of the vaccine.The other great hazard of war that was brought under control in World War I was tetanus. This was achieved by the prophylactic injection of tetanus antitoxin into all wounded men. The serum was originally prepared by the bacteriologists Emil von Behring (Behring, Emil von) and Shibasaburo Kitasato in 1890–92, and the results of this first large-scale trial amply confirmed its efficacy. (Tetanus antitoxin is a sterile solution of antibody globulins—a type of blood protein—from immunized horses or cattle.)It was not until the 1930s, however, that an efficient vaccine, or toxoid, as it is known in the cases of tetanus and diphtheria, was produced against tetanus. (Tetanus toxoid is a preparation of the toxin—or poison—produced by the microorganism; injected into humans, it stimulates the body's own defenses against the disease, thus bringing about immunity.) Again, a war was to provide the opportunity for testing on a large scale, and experience with tetanus toxoid in World War II indicated that it gave a high degree of protection.The story of diphtheria is comparable to that of tetanus, though even more dramatic. First, as with tetanus antitoxin, came the preparation of diphtheria antitoxin by Behring and Kitasato in 1890. As the antitoxin came into general use for the treatment of cases, the death rate began to decline. There was no significant fall in the number of cases, however, until a toxin–antitoxin mixture, introduced by Behring in 1913, was used to immunize children. A more effective toxoid was introduced by the French bacteriologist Gaston Ramon in 1923, and with subsequent improvements this became one of the most effective vaccines available in medicine. Where mass immunization of children with the toxoid was practiced, as in the United States and Canada beginning in the late 1930s and in England and Wales in the early 1940s, cases of diphtheria and deaths from the disease became almost nonexistent. In England and Wales, for instance, the number of deaths fell from an annual average of 1,830 in 1940–44 to zero in 1969. Administration of a combined vaccine against diphtheria, pertussis (whooping cough), and tetanus (DPT) is recommended for young children. Although an increasing number of dangerous side effects from the DPT vaccine have been reported, it continues to be used in most countries because of the protection it affords.BCG vaccine for tuberculosisIf, as is universally accepted, prevention is better than cure, immunization is the ideal way of dealing with diseases caused by microorganisms. An effective, safe vaccine protects the individual from disease, whereas chemotherapy merely copes with the infection once the individual has been affected. In spite of its undoubted value, however, immunization has been a recurring source of dispute. Like vaccination against typhoid (and against poliomyelitis later), tuberculosis immunization evoked widespread contention.In 1908 Albert Calmette (Calmette, Albert), a pupil of Pasteur, and Camille Guérin (Guérin, Camille) produced an avirulent (weakened) strain of the tubercle bacillus. About 13 years later, vaccination of children against tuberculosis was introduced, with a vaccine made from this avirulent strain and known as BCG (bacillus Calmette-Guérin) vaccine. Although it was adopted in France, Scandinavia, and elsewhere, British and U.S. authorities frowned upon its use on the grounds that it was not safe and that the statistical evidence in its favour was not convincing.One of the stumbling blocks in the way of its widespread adoption was what came to be known as the Lübeck disaster. In the spring of 1930, 249 infants were vaccinated with BCG vaccine in Lübeck, Ger.; by autumn, 73 of the 249 were dead. Criminal proceedings were instituted against those responsible for giving the vaccine. The final verdict was that the vaccine had been contaminated, and the BCG vaccine itself was exonerated from any responsibility for the deaths. A bitter controversy followed, but in the end the protagonists of the vaccine won when a further trial showed that the vaccine was safe and that it protected four out of five of those vaccinated.Immunization against viral diseasesWith the exception of smallpox, it was not until well into the 20th century that efficient viral vaccines became available. In fact, it was not until the 1930s that much began to be known about viruses. The two developments that contributed most to the rapid growth in knowledge after that time were the introduction of tissue culture as a means of growing viruses in the laboratory and the availability of the electron microscope. Once the virus could be cultivated with comparative ease in the laboratory, the research worker could study it with care and evolve methods for producing one of the two requirements for a safe and effective vaccine: either a virus that was so attenuated, or weakened, that it could not produce the disease for which it was responsible in its normally virulent form; or a killed virus that retained the faculty of inducing a protective antibody response in the vaccinated individual.The first of the viral vaccines to result from these advances was for yellow fever, developed by the microbiologist Max Theiler in the late 1930s. About 1945 the first relatively effective vaccine was produced for influenza; (influenza) in 1954 the American physician Jonas E. Salk (Salk, Jonas Edward) introduced a vaccine (polio vaccine) for poliomyelitis (polio); and in 1960 an oral poliomyelitis (polio) vaccine, developed by the virologist Albert B. Sabin (Sabin, Albert Bruce), came into wide use.These vaccines went far toward bringing under control three of the major diseases of the time although, in the case of influenza, a major complication is the disturbing proclivity of the virus to change its character from one epidemic to another. Even so, sufficient progress has been made to ensure that a pandemic like the one that swept the world in 1918–19, killing more than 15,000,000 people, is unlikely to occur again. Centres are now equipped to monitor outbreaks of influenza throughout the world in order to establish the identity of the responsible viruses and, if necessary, take steps to produce appropriate vaccines.During the 1960s effective vaccines came into use for measles and rubella (German measles). Both evoked a certain amount of controversy. In the case of measles in the Western world it was contended that, if acquired in childhood, it is not a particularly hazardous malady, and the naturally acquired disease evokes permanent immunity in the vast majority of cases. Conversely, the vaccine induces a certain number of adverse reactions, and the duration of the immunity it produces is problematical. In the end the official view was that universal measles vaccination is to be commended.The situation with rubella vaccination (vaccine) was different. This is a fundamentally mild affliction, and the only cause for anxiety is its proclivity to induce congenital deformities if a pregnant woman should acquire the disease. Once an effective vaccine was available, the problem was the extent to which it should be used. Ultimately the consensus was reached that all girls who had not already had the disease should be vaccinated (inoculation) at about 12 years. In the United States children are routinely immunized against measles, mumps, and rubella at the age of 15 months.The immune responseWith advances in cell biology in the second half of the 20th century came a more profound understanding of both normal and abnormal conditions in the body. Electron microscopy enabled observers to peer more deeply into the structures of the cell, and chemical investigations revealed clues to their functions in the cell's intricate metabolism. The overriding importance of the nuclear genetic material DNA (deoxyribonucleic acid) in regulating the cell's protein and enzyme production lines became evident. A clearer comprehension also emerged of the ways in which the cells of the body defend themselves by modifying their chemical activities to produce antibodies against injurious agents.Up until the turn of the century, immunity referred mostly to the means of resistance of an animal to invasion by a parasite or microorganism. Around mid-century there arose a growing realization that immunity and immunology cover a much wider field and are concerned with mechanisms for preserving the integrity of the individual. The introduction of organ transplantation (transplant), with its dreaded complication of tissue rejection, brought this broader concept of immunology to the fore.At the same time, research workers and clinicians began to appreciate the far-reaching implications of immunity in relation to endocrinology, genetics, tumour biology, and the biology of a number of other maladies. The so-called autoimmune diseases are caused by an aberrant series of immune responses by which the body's own cells are attacked. Suspicion is growing that a number of major disorders such as diabetes, rheumatoid arthritis, and multiple sclerosis may be caused by similar mechanisms.In some conditions viruses invade the genetic material of cells and distort their metabolic processes. Such viruses may lie dormant for many years before becoming active. This may be the underlying cause of many cancers, in which cells escape from the usual constraints imposed upon them by the normal body. The dreaded affliction of acquired immune deficiency syndrome (AIDS) is caused by a virus that has a long dormant period and then attacks the cells that produce antibodies. The result is that the affected person is not able to generate an immune response to infections or malignancies.At the beginning of the 20th century, endocrinology was in its infancy. Indeed, it was not until 1905 that Ernest H. Starling, one of the many brilliant pupils of Edward Sharpey-Schafer, the dean of British physiology during the early decades of the century, introduced the term hormone for the internal secretions of the endocrine glands. In 1891 the English physician George Redmayne Murray achieved the first success in treating myxedema (the common form of hypothyroidism) with an extract of the thyroid gland. Three years later, Sharpey-Schafer (Sharpey-Schafer, Sir Edward Albert) and George Oliver demonstrated in extracts of the adrenal glands a substance that raised the blood pressure; and in 1901 Jokichi Takamine (Takamine, Jokichi), a Japanese chemist working in the United States, isolated this active principle, known as epinephrine (epinephrine and norepinephrine) or adrenaline.During the first two decades of the century, steady progress was made in the isolation, identification, and study of the active principles of the various endocrine glands, but the outstanding event of the early years was the discovery of insulin by Frederick Banting (Banting, Sir Frederick Grant), Charles H. Best (Best, Charles H.), and J.J.R. Macleod (Macleod, J.J.R.) in 1921. Almost overnight the lot of the diabetic (diabetes mellitus) patient changed from a sentence of almost certain death to a prospect not only of survival but of a long and healthy life.For more than 30 years, some of the greatest minds in physiology had been seeking the cause of diabetes mellitus. In 1889 the German physicians Joseph von Mering and Oskar Minkowski had shown that removal of the pancreas in dogs produced the disease. In 1901 the American pathologist Eugene L. Opie described degenerative changes in the clumps of cells in the pancreas known as the islets of Langerhans (Langerhans, islets of), thus confirming the association between failure in the function of these cells and diabetes. Sharpey-Schafer concluded that the islets of Langerhans secrete a substance that controls the metabolism of carbohydrate. Then Banting, Best, and Macleod, working at the University of Toronto, succeeded in isolating the elusive hormone and gave it the name insulin.Insulin was available in a variety of forms, but synthesis on a commercial scale was not achieved, and the only source of the hormone was the pancreas of animals. One of its practical disadvantages is that it has to be given by injection; consequently an intense search was conducted for some alternative substance that would be active when taken by mouth. Various preparations—oral hypoglycemic agents, as they are known—appeared that were effective to a certain extent in controlling diabetes, but evidence indicated that these were only of value in relatively mild cases of the disease. For the person with advanced diabetes, a normal, healthy life remained dependent upon the continuing use of insulin injections.Another major advance in endocrinology came from the Mayo Clinic, in Rochester, Minn. In 1949 Philip S. Hench (Hench, Philip Showalter) and his colleagues announced that a substance isolated from the cortex of the adrenal gland had a dramatic effect upon rheumatoid arthritis. This was compound E, or cortisone, as it came to be known, which had been isolated by Edward C. Kendall (Kendall, Edward Calvin) in 1935. Cortisone and its many derivatives proved to be potent as anti-inflammatory agents. Although it is not a cure for rheumatoid arthritis, as a temporary measure cortisone can often control the acute exacerbation caused by the disease and can provide relief in other conditions, such as acute rheumatic fever, certain kidney diseases, certain serious diseases of the skin, and some allergic conditions, including acute exacerbations of asthma. Of even more long-term importance is the valuable role it has as a research tool.Sex hormones (sex hormone)Not the least of the advances in endocrinology was the increasing knowledge and understanding of the sex hormones. This culminated in the application of this knowledge to the problem of birth control. After an initial stage of hesitancy, the contraceptive (contraception) pill, with its basic rationale of preventing ovulation, was accepted by the vast majority of family-planning organizations and many gynecologists as the most satisfactory method of contraception. Its risks, practical and theoretical, introduced a note of caution, but this was not sufficient to detract from the wide appeal induced by its effectiveness and ease of use.VitaminsIn the field of nutrition (nutrition, human), the outstanding advance of the 20th century was the discovery and the appreciation of the importance to health of the “accessory food factors,” or vitamins (vitamin). Various workers had shown that animals did not thrive on a synthetic diet containing all the correct amounts of protein, fat, and carbohydrate; they even suggested that there must be some unknown ingredients in natural food that were essential for growth and the maintenance of health. But little progress was made in this field until the classical experiments of the English biologist F. Gowland Hopkins (Hopkins, Sir Frederick Gowland) were published in 1912. These were so conclusive that there could be no doubt that what he termed “accessory substances” were essential for health and growth.The name vitamine was suggested for these substances by the biochemist Casimir Funk in the belief that they were amines, certain compounds derived from ammonia. In due course, when it was realized that they were not amines, the term was altered to vitamin.Once the concept of vitamins was established on a firm scientific basis it was not long before their identity began to be revealed. Soon there was a long series of vitamins, best known by the letters of the alphabet after which they were originally named when their chemical identity was still unknown. By supplementing the diet with foods containing particular vitamins, deficiency diseases such as rickets (due to deficiency of vitamin D) and scurvy (due to lack of vitamin C, or ascorbic acid) practically disappeared from Western countries, while deficiency diseases such as beriberi (caused by lack of vitamin B1, or thiamine), which were endemic in Eastern countries, either disappeared or could be remedied with the greatest of ease.The isolation of vitamin B12, or cyanocobalamin (vitamin B12), was of particular interest because it almost rounded off the fascinating story of how pernicious anemia was brought under control. Throughout the first two decades of the century, the diagnosis of pernicious anemia, like that of diabetes mellitus, was nearly equivalent to a death sentence. Unlike the more common form of so-called secondary anemia, it did not respond to the administration of suitable iron salts, and no other form of treatment touched it; hence, the grimly appropriate title of pernicious anemia.In the early 1920s, George R. Minot (Minot, George Richards), one of the many brilliant investigators that Harvard University has contributed to medical research, became interested in work being done by the American pathologist George H. Whipple (Whipple, George H.) on the beneficial effects of raw beef liver in severe experimental anemia. With a Harvard colleague, William P. Murphy (Murphy, William P.), he decided to investigate the effect of raw liver in patients with pernicious anemia, and in 1926 they were able to announce that this form of therapy was successful. The validity of their findings was amply confirmed, and the fear of pernicious anemia came to an end.As so often happens in medicine, many years were to pass before the rationale of liver therapy in pernicious anemia was fully understood. In 1948, however, almost simultaneously in the United States and Britain, the active principle, cyanocobalamin, was isolated from liver, and this vitamin became the standard treatment for pernicious anemia.Malignant diseaseWhile progress was the hallmark of medicine after the beginning of the 20th century, there is one field in which a gloomier picture must be painted, that of malignant disease, or cancer. It is the second most common cause of death in most Western countries in the second half of the 20th century, being exceeded only by deaths from heart disease. Some progress, however, has been achieved. The causes of the various types of malignancies are not known, but many more methods are available for attacking the problem; surgery remains the principal therapeutic standby, but radiotherapy and chemotherapy are increasingly used.Soon after the discovery of radium was announced, in 1898, its potentialities in treating cancer were realized; in due course it assumed an important role in therapy. Simultaneously, deep X-ray therapy was developed, and with the atomic age came the use of radioactive isotopes (radioactive isotope). (A radioactive (radiation) isotope is an unstable variant of a substance that has a stable form; during the process of breaking down, the unstable form emits radiation.) High-voltage X-ray therapy and radioactive isotopes have largely replaced radium. Whereas irradiation long depended upon X rays generated at 250 kilovolts, machines that are capable of producing X rays generated at 8,000 kilovolts and betatrons of up to 22,000,000 electron volts (MeV) have come into clinical use.The most effective of the isotopes is radioactive cobalt. Telecobalt machines (those that hold the cobalt at a distance from the body) are available containing 2,000 curies or more of the isotope, an amount equivalent to 3,000 grams of radium and sending out a beam equivalent to that from a 3,000-kilovolt X-ray machine.Of even more significance have been the developments in the chemotherapy of cancer. Nothing remotely resembling a chemotherapeutic cure has been achieved, but in certain forms of malignant disease, such as leukemia, which cannot be treated by surgery, palliative effects have been achieved that prolong life and allow the patient in many instances to lead a comparatively normal existence.Fundamentally, however, perhaps the most important advance of all in this field has been the increasing appreciation of the importance of prevention. The discovery of the relationship between cigarette smoking and lung cancer is the classic example. Less publicized, but of equal import, is the continuing supervision of new techniques in industry and food manufacture in an attempt to ensure that they do not involve the use of cancer-causing substances.The first half of the 20th century witnessed the virtual conquest of three of the major diseases of the tropics: malaria, yellow fever, and leprosy. At the turn of the century, as for the preceding two centuries, quinine was the only known drug to have any appreciable effect on malaria. With the increasing development of tropical countries and rising standards of public health, it became obvious that quinine was not completely satisfactory. Intensive research between World Wars I and II indicated that several synthetic compounds were more effective. The first of these to become available, in 1934, was quinacrine (known as mepacrine, Atabrine, or Atebrin). In World War II it amply fulfilled the highest expectations and helped to reduce disease among Allied troops in Africa, Southeast Asia, and the Far East. A number of other effective antimalarial drugs subsequently became available.An even brighter prospect—the virtual eradication of malaria—was opened up by the introduction, during World War II, of the insecticide DDT (1,1,1-trichloro-2,2,-bis[p-chlorophenyl]ethane, or dichlorodiphenyltrichloro-ethane). It had long been realized that the only effective way of controlling malaria was to eradicate the anopheline mosquitoes (mosquito) that transmit the disease. Older methods of mosquito control, however, were cumbersome and expensive. The lethal effect of DDT on the mosquito, its relative cheapness, and its ease of use on a widespread scale provided the answer. An intensive worldwide campaign, sponsored by the World Health Organization, was planned and went far toward bringing malaria under control.The major problem encountered with respect to effectiveness was that the mosquitoes were able to develop a resistance to DDT; but the introduction of other insecticides, such as dieldrin and lindane (BHC), helped to overcome this difficulty. In recent years the use of these and other insecticides has been strongly criticized by ecologists, however.Yellow fever is another mosquito-transmitted disease, and the prophylactic value of modern insecticides in its control was almost as great as in the case of malaria. The forest reservoirs of the virus present a more difficult problem, but the combined use of immunization and insecticides did much to bring this disease under control.Until the 1940s the only drugs available for treating leprosy were the chaulmoogra oils and their derivatives. These, though helpful, were far from satisfactory. In the 1940s the group of drugs known as the sulfones (sulfone) appeared, and it soon became apparent that they were infinitely better than any other group of drugs in the treatment of leprosy. Several other drugs later proved promising. Although there is as yet no known cure—in the strict sense of the term—for leprosy, the outlook has so changed that there are good grounds for believing that this age-old scourge can be brought under control and the victims of the disease saved from those dreaded mutilations that have given leprosy such a fearsome reputation throughout the ages.William Archibald Robson Thomson Philip RhodesSurgery in the 20th centuryThe opening phaseThree seemingly insuperable obstacles beset the surgeon in the years before the mid-19th century: pain, infection, and shock. Once these were overcome, the surgeon believed that he could burst the bonds of centuries and become the master of his craft. There is more, however, to anesthesia (anesthetic) than putting the patient to sleep. Infection, despite first antisepsis (destruction of microorganisms present) and later asepsis (avoidance of contamination), is still an ever-present menace; and shock continues to perplex physicians. But in the 20th century, surgery has progressed farther, faster, and more dramatically than in all preceding ages.The situation encounteredThe shape of surgery that entered the new century was clearly recognizable as the forerunner of today's, blurred and hazy though the outlines may now seem. The operating theatre still retained an aura of the past, when the surgeon played to his audience and the patient was little more than a stage prop. In most hospitals it was a high room lit by a skylight, with tiers of benches rising above the narrow, wooden operating table. The instruments, kept in glazed or wooden cupboards around the walls, were of forged steel, unplated, and with handles of wood or ivory.The means to combat infection hovered between antisepsis (antiseptic) and asepsis. Instruments and dressings were mostly sterilized by soaking them in dilute carbolic acid (or other antiseptic), and the surgeon often endured a gown freshly wrung out in the same solution. Asepsis gained ground fast, however. It had been born in the Berlin clinic of Ernst von Bergmann where, in 1886, steam sterilization had been introduced. Gradually, this led to the complete aseptic ritual, which has as its basis the bacterial cleanliness (as opposed to social cleanliness) of everything that comes in contact with the wound. Hermann Kümmell, of Hamburg, devised the routine of “scrubbing up.” In 1890 William Stewart Halsted, of Johns Hopkins University, had rubber gloves specially made for operating, and in 1896 Johannes von Mikulicz-Radecki, a Pole working at Breslau, Ger., invented the gauze mask.Many surgeons, brought up in a confused misunderstanding of the antiseptic principle—believing that carbolic would cover a multitude of sins, many of which they were ignorant of committing—failed to grasp what asepsis was all about. Thomas Annandale, for example, blew through his catheters to make sure that they were clear, and many an instrument, dropped accidentally, was simply given a quick wipe and returned to use. Tradition died hard, and asepsis had an uphill struggle before it was fully accepted. “I believe firmly that more patients have died from the use of gloves than have ever been saved from infection by their use,” wrote W.P. Carr, an American, in 1911. Over the years, however, a sound technique was evolved as the foundation for the growth of modern surgery.Anesthesia, at the turn of the century, progressed slowly. Few physicians made a career of the subject, and frequently the patient was rendered unconscious by a student, a nurse, or a porter wielding a rag and bottle. Chloroform was overwhelmingly more popular than ether, on account of its ease of administration, despite the fact that it was liable to kill by stopping the heart.Although by the end of the first decade, nitrous oxide (laughing gas) combined with ether had displaced—but by no means entirely—the use of chloroform, the surgical problems were far from ended. For years to come the abdominal surgeon besought the anesthetist to deepen the level of anesthesia and thus relax the abdominal muscles; the anesthetist responded to the best of his ability, acutely aware that the deeper he went, the closer the patient was to death. When other anesthetic agents were discovered, the anesthetist came into his own, and many advances in spheres such as brain and heart surgery would have been impossible without his skill.The third obstacle, shock, is perhaps the most complex and the most difficult to define satisfactorily. The only major cause properly appreciated at the start of the 20th century was loss of blood, and once that had occurred nothing, in those days, could be done. And so, the study of shock—its causes, its effects on human physiology, and its prevention and treatment—became all-important to the progress of surgery.In the latter part of the 19th century, then, surgeons had been liberated from the age-old bogies of pain, pus, and hospital gangrene. Hitherto, operations had been restricted to amputations, cutting for stone in the bladder, tying off arterial aneurysms (bulging and thinning of artery walls), repairing hernias, and a variety of procedures that could be done without going too deeply beneath the skin. But the anatomical knowledge, a crude skill derived from practice on dead bodies, and above all the enthusiasm, were there waiting. Largely ignoring the mass of problems they uncovered, surgeons launched forth into an exploration of the human body.They acquired a reputation for showmanship; but much of their surgery, though speedy and spectacular, was rough and ready. There were a few who developed supreme skill and dexterity and could have undertaken a modern operation with but little practice; indeed, some devised the very operations still in use today. One such was Theodor Billroth (Billroth, Theodor), head of the surgical clinic at Vienna, who collected a formidable list of successful “first” operations. He represented the best of his generation—a surgical genius, an accomplished musician, and a kind, gentle man who brought the breath of humanity to his work. Moreover, the men he trained, including von Mikulicz, Vincenz Czerny, and Anton von Eiselsberg, consolidated the brilliant start that he had given to abdominal surgery in Europe.Changes before World War IThe opening decade of the 20th century was a period of transition. Flamboyant exhibitionism was falling from favour as surgeons, through experience, learned the merits of painstaking, conscientious operation—treating the tissues gently and carefully controlling every bleeding point. The individualist was not submerged, however, and for many years the development of the various branches of surgery rested on the shoulders of a few clearly identifiable men. Teamwork on a large scale arrived only after World War II. The surgeon, at first, was undisputed master in his own wards and theatre. But as time went on and he found he could not solve his problems alone, he called for help from specialists in other fields of medicine and, even more significantly, from his colleagues in other scientific disciplines.The increasing scope of surgery led to specialization. Admittedly, most general surgeons had a special interest, and for a long time there had been an element of specialization in such fields as ophthalmology, orthopedics, obstetrics, and gynecology; but before long it became apparent that, to achieve progress in certain areas, surgeons had to concentrate their attention on that particular subject.By the start of the 20th century, abdominal surgery, which provided the general surgeon with the bulk of his work, had grown beyond infancy, thanks largely to Billroth. In 1881 he had performed the first successful removal of part of the stomach for cancer. His next two cases were failures, and he was stoned in the streets of Vienna. Yet, he persisted and by 1891 had carried out 41 more of these operations with 16 deaths—a remarkable achievement for that era.Peptic ulcers (peptic ulcer) (gastric and duodenal) appeared on the surgical scene (perhaps as a new disease, but more probably because they had not been diagnosed previously), and in 1881 Ludwig Rydygier cured a young woman of her gastric ulcer by removing it. Bypass operations—gastroenterostomies—soon became more popular, however, and enjoyed a vogue that lasted into the 1930s, even though fresh ulcers at the site of the juncture were not uncommon.The other end of the alimentary tract was also subjected to surgical intervention; cancers were removed from the large bowel and rectum with mortality rates that gradually fell from 80 to 60 to 20 to 12 percent as the surgeons developed their skill. In 1908 the British surgeon Ernest Miles carried out the first abdominoperineal resection for cancer of the rectum; that is, the cancer was attacked both from the abdomen and from below through the perineum (the area between the anus and the genitals), either by one surgeon, who actually did two operations, or by two working together. This technique formed the basis for all future developments.Much of the new surgery in the abdomen was for cancer, but not all. Appendectomy became the accepted treatment for appendicitis (in appropriate cases) in the United States before the close of the 19th century; but in Great Britain surgeons were reluctant to remove the organ until 1902, when King Edward VII's (Edward VII) coronation was dramatically postponed on account of his appendicitis. The publicity attached to his operation caused the disease and its surgical treatment to become fashionable—despite the fact that the royal appendix remained in the King's abdomen; the surgeon, Frederic Treves, had merely drained the abscess.Though probably the most demanding of all the surgical specialties, neurosurgery was nevertheless one of the first to emerge. The techniques and principles of general surgery were inadequate for work in such a delicate field. William Macewen, a Scottish general surgeon of outstanding versatility, and Victor Alexander Haden Horsley (Horsley, Sir Victor), the first British neurosurgeon, showed that the surgeon had much to offer in the treatment of disease of the brain and spinal cord. Macewen, in 1893, recorded 19 patients operated on for brain abscess, 18 of whom were cured; at that time most other surgeons had 100 percent mortality rates for the condition. His achievement remained unequaled until the discovery of penicillin.An American, Harvey Williams Cushing (Cushing, Harvey Williams), almost by himself consolidated neurosurgery as a specialty. From 1905 on, he advanced neurosurgery through a series of operations and through his writings. Tumours, epilepsy, trigeminal neuralgia, and pituitary disorders were among the conditions he treated successfully.In 1895 a development at the University of Würzburg had far-reaching effects on medicine and surgery, opening up an entirely fresh field of the diagnosis and study of disease and leading to a new form of treatment, radiation therapy. This was the discovery of X rays by Wilhelm Conrad Röntgen, a professor of physics. Within months of the discovery there was an extensive literature on the subject: Robert Jones, a British surgeon, had localized a bullet in a boy's wrist before operating; stones in the urinary bladder and gallbladder had been demonstrated; and fractures had been displayed.Experiments began on introducing substances that are opaque to X rays into the body to reveal organs and formations, both normal and abnormal. Walter Cannon, a Boston physiologist, used X rays in 1898 in his studies of the alimentary tract. Friedrich Voelcker, of Heidelberg, devised retrograde pyelography (introduction of the radiopaque medium into the kidney pelvis by way of the ureter) for the study of the urinary tract in 1905; in Paris in 1921, Jean Sicard X-rayed the spinal canal with the help of an oily iodine substance, and the next year he did the same for the bronchial tree; and in 1924 Evarts Graham, of St. Louis, used a radiopaque contrast medium to view the gallbladder. Air was also used to provide contrast; in 1918, at Johns Hopkins, Walter Dandy injected air into the ventricles (liquid-filled cavities) of the brain.The problems of injecting contrast media into the blood vessels took longer to solve, and it was not until 1927 that António Moniz, of Lisbon, succeeded in obtaining pictures of the arteries of the brain. Eleven years later, George Robb and Israel Steinberg of New York overcame some of the difficulties of cardiac catheterization (introduction of a small tube into the heart by way of veins or arteries) and were able to visualize the chambers of the heart on X-ray film. After much research, a further refinement came in 1962, when Frank Sones and Earl K. Shirey of Cleveland showed how to introduce the contrast medium into the coronary arteries.The battlefields of the 20th century stimulated the progress of surgery and taught the surgeon innumerable lessons, which were subsequently applied in civilian practice. Regrettably, though, the principles of military surgery and casualty evacuation, which can be traced back to the Napoleonic wars, had to be learned over again.World War I broke, quite dramatically, the existing surgical hierarchy and rule of tradition. No longer did the European surgeon have to waste his best years in apprenticeship before seating himself in his master's chair. Suddenly, young surgeons in the armed forces began confronting problems that would have daunted their elders. Furthermore, their training had been in “clean” surgery performed under aseptic conditions. Now they found themselves faced with the need to treat large numbers of grossly contaminated wounds (wound) in improvised theatres. They rediscovered debridement (the surgical excision of dead and dying tissue and the removal of foreign matter).The older surgeons cried “back to Lister,” but antiseptics, no matter how strong, were no match for putrefaction and gangrene. One method of antiseptic irrigation—devised by Alexis Carrel (Carrel, Alexis) and Henry Dakin and called the Carrel–Dakin treatment (Dakin's solution)—was, however, beneficial, but only after the wound had been adequately debrided. The scourges of tetanus and gas gangrene were controlled to a large extent by antitoxin and antiserum injections, yet surgical treatment of the wound remained an essential requirement.Abdominal casualties fared badly for the first year of the war, because experience in the utterly different circumstances of the South African War had led to a belief that these men were better left alone surgically. Fortunately, the error of continuing with such a policy 15 years later was soon appreciated, and every effort was made to deliver the wounded men to a suitable surgical unit with all speed. Little progress was made with chest wounds beyond opening up the wound even further to drain pus from the pleural cavity between the chest wall and the lungs.Perhaps the most worthwhile and enduring benefit to flow from World War I was rehabilitation (physical medicine and rehabilitation). For almost the first time, surgeons realized that their work did not end with a healed wound. In 1915 Robert Jones set up special facilities for orthopedic patients, and at about the same time Harold Gillies founded British plastic surgery in a hut at Sidcup, Kent. In 1917 Gillies popularized the pedicle type of skin graft (the type of graft in which skin and subcutaneous tissue are left temporarily attached for nourishment to the site from which the graft was taken). Since then plastic surgery has given many techniques and principles to other branches of surgery.Between the world warsThe years between the two world wars may conveniently be regarded as the time when surgery consolidated its position. A surprising number of surgical firsts and an amazing amount of fundamental research had been achieved even in the late 19th century, but the knowledge and experience could not be converted to practical use because the human body could not survive the onslaught. In the years between World Wars I and II, it was realized that physiology—in its widest sense, including biochemistry and fluid and electrolyte balance—was of major importance along with anatomy, pathology, and surgical technique.The problem of shockThe first problem to be tackled was shock, which was, in brief, found to be due to a decrease in the effective volume of the circulation. To combat shock, the volume had to be restored, and the obvious substance was blood itself. In 1901 Karl Landsteiner, then in Austria, discovered the ABO blood groups, and in 1914 sodium citrate was added to freshly drawn blood (blood transfusion) to prevent clotting. Blood was occasionally transfused during World War I, but three-quarters of a pint was considered a large amount. These transfusions were given by directly linking the vein of a donor with that of the recipient. The continuous drip method, in which blood flows from a flask, was introduced by Hugh Marriott and Alan Kekwick at the Middlesex Hospital, London, in 1935.As blood transfusions increased in frequency and volume, blood banks were required. Although it took another world war before these were organized on a large scale, the first tentative steps were taken by Sergey Sergeyevich Yudin, of Moscow, who, in 1933, used cadaver blood, and by Bernard Fantus, of Chicago, who, four years later, used living donors as his source of supply. Saline solution, plasma, artificial plasma expanders, and other solutions are now also used in the appropriate circumstances.Sometimes after operations (especially abdominal operations), the gut becomes paralyzed. It is distended, and quantities of fluid pour into it, dehydrating (dehydration) the body. In 1932 Owen Wangensteen, at the University of Minnesota, advised decompressing the bowel, and in 1934 two other Americans, Thomas Miller and William Abbott, of Philadelphia, invented an apparatus for this purpose, a tube with an inflatable balloon on the end that could be passed into the small intestine. The fluid lost from the tissues was replaced by a continuous intravenous drip of saline solution on the principle described by Rudolph Matas, of New Orleans, in 1924. These techniques dramatically improved abdominal surgery, especially in cases of obstruction, peritonitis (inflammation of the abdominal membranes), and acute emergencies generally, since they made it possible to keep the bowel empty and at rest.Anesthesia and thoracic surgeryThe strides taken in anesthesia from the 1920s onward allowed surgeons much more freedom. Rectal anesthesia had never proved satisfactory, and the first improvement on the combination of nitrous oxide, oxygen, and ether was the introduction of the general anesthetic cyclopropane by Ralph Waters of Madison, Wis., in 1933. Soon afterward, intravenous anesthesia was introduced; John Lundy of the Mayo Clinic brought to a climax a long series of trials by many workers when he used Pentothal (thiopental sodium, a barbiturate) to put a patient peacefully to sleep. Then, in 1942, Harold Griffith and G. Enid Johnson, of Montreal, produced muscular paralysis by the injection of a purified preparation of curare. This was harmless since, by then, the anesthetist was able to control the patient's respiration.If there was one person who was aided more than any other by the progress in anesthesia, it was the thoracic (chest) surgeon. What had bothered him previously was the collapse of the lung, which occurred whenever the pleural cavity was opened. Since the end of the 19th century, many and ingenious methods had been devised to prevent this from happening. The best known was the negative pressure cabinet of Ernst Ferdinand Sauerbruch, then at Mikulicz' clinic at Breslau; the cabinet was first demonstrated in 1904 but was destined soon to become obsolete.The solution lay in inhalational anesthesia administered under pressure. Indeed, when Théodore Tuffier, in 1891, successfully removed the apex of a lung for tuberculosis, this was the technique that he used; he even added an inflatable cuff around the tube inserted in the trachea to ensure a gas-tight fit. Tuffier was ahead of his time, however, and other surgeons and research workers wandered into confused and complex byways before Ivan Magill and Edgar Rowbotham, working at Gillies' plastic-surgery unit, found their way back to the simplicity of the endotracheal tube and positive pressure. In 1931 Ralph Waters showed that respiration (respiratory disease) could be controlled either by squeezing the anesthetic bag by hand or by using a small motor.These advances allowed thoracic surgery to move into modern times. In the 1920s, operations had been performed mostly for infective conditions and as a last resort. The operations necessarily were unambitious and confined to collapse therapy, including thoracoplasty (removal of ribs), apicolysis (collapse of a lung apex and artificially filling the space), and phrenic crush (which paralyzed the diaphragm on the chosen side); to isolation of the area of lung to be removed by first creating pleural adhesions; and to drainage.The technical problems of surgery within the chest were daunting until Harold Brunn of San Francisco reported six lobectomies (removals of lung lobes) for bronchiectasis with only one death. (In bronchiectasis one or more bronchi or bronchioles are chronically dilated and inflamed, with copious discharge of mucus mixed with pus.) The secret of Brunn's success was the use of intermittent suction after surgery to keep the cavity free of secretions until the remaining lobes of the lung could expand to fill the space. In 1931 Rudolf Nissen, in Berlin, removed an entire lung from a girl with bronchiectasis. She recovered to prove that the risks were not as bad as had been feared.cancer of the lung has become a major disease of the 20th century; perhaps it has genuinely increased, or perhaps modern techniques of diagnosis reveal it more often. As far back as 1913 a Welshman, Hugh Davies, removed a lower lobe for cancer, but a new era began when Evarts Graham removed a whole lung for cancer in 1933. The patient, a doctor, was still alive at the time of Graham's death in 1957.The thoracic part of the esophagus is particularly difficult to reach, but in 1909 the British surgeon Arthur Evans successfully operated on it for cancer. But results were generally poor until, in 1944, John Garlock, of New York, showed that it is possible to excise the esophagus and to bring the stomach up through the chest and join it to the pharynx. Lengths of colon are also used as grafts to bridge the gap.World War II and afterOnce the principles of military surgery were relearned and applied to modern warfare, instances of death, deformity, and loss of limb were reduced to levels previously unattainable. This was due largely to a thorough reorganization of the surgical services, adapting them to prevailing conditions, so that casualties received the appropriate treatment at the earliest possible moment. Evacuation by air (first used in World War I) helped greatly in this respect. Diagnostic facilities were improved, and progress in anesthesia (anesthetic) kept pace with the surgeon's demands. Blood was transfused in adequate—and hitherto unthinkable—quantities, and the blood transfusion service as it is known today came into being.Surgical specialization and teamwork reached new heights with the creation of units to deal with the special problems of injuries to different parts of the body. But the most revolutionary change was in the approach to wound infections brought about by the use of sulfonamides and (after 1941) of penicillin. The fact that these drugs could never replace meticulous wound surgery was, however, another lesson learned only in the bitter school of experience.When the war ended, surgeons returned to civilian life feeling that they were at the start of a completely new, exciting era; and indeed they were, for the intense stimulation of the war years had led to developments in many branches of science that could now be applied to surgery. Nevertheless, it must be remembered that these developments merely allowed surgeons to realize the dreams of their fathers and grandfathers; they opened up remarkably few original avenues. The two outstanding phenomena of the 1950s and 1960s—heart surgery and organ transplantation—both originated in a real and practical manner at the turn of the century.Support from other technologiesAt first, perhaps, the surgeon tried to do too much himself, but before long his failures taught him to share his problems with experts in other fields. This was especially so with respect to difficulties of biomedical engineering and the exploitation of new materials. The relative protection from infection given by antibiotics and chemotherapy allowed the surgeon to become far more adventurous than hitherto in repairing and replacing damaged or worn-out tissues with foreign materials. Much research was still needed to find the best material for a particular purpose and to make sure that it would be acceptable to the body.Plastics (plastic), in their seemingly infinite variety, have come to be used for almost everything from suture material to heart valves; for strengthening the repair of hernias; for replacement of the head of the femur (first done by the French surgeon Jean Judet and his brother Robert-Louis Judet in 1950); for replacement of the lens of the eye after extraction of the natural lens for cataract; for valves to drain fluid from the brain in patients with hydrocephalus; and for many other applications. This is a far cry, indeed, from the unsatisfactory use of celluloid to restore bony defects of the face by the German surgeon Fritz Berndt in the 1890s. Inert metals, such as vitallium, have also found a place in surgery, largely in orthopedics for the repair of fractures and the replacement of joints.The scope of surgery (microsurgery) was further expanded by the introduction of the operating microscope. This brought the benefit of magnification particularly to neurosurgery and to ear surgery. In the latter it opened up a whole field of operations on the eardrum and within the middle ear (ear bone). The principles of these operations were stated in 1951 and 1952 by two German surgeons, Fritz Zöllner and Horst Wullstein; and in 1952 Samuel Rosen of New York mobilized the footplate of the stapes to restore hearing in otosclerosis—a procedure attempted by the German Jean Kessel in 1876.Although surgeons aim to preserve as much of the body as disease permits, they are sometimes forced to take radical measures to save life; when, for instance, cancer affects the pelvic organs. Pelvic exenteration (surgical removal of the pelvic organs and nearby structures) in two stages was devised by Allen Whipple of New York City, in 1935, and in one stage by Alexander Brunschwig, of Chicago, in 1937. Then, in 1960, Charles S. Kennedy, of Detroit, after a long discussion with Brunschwig, put into practice an operation that he had been considering for 12 years: hemicorporectomy—surgical removal of the lower part of the body. The patient died on the 11th day. The first successful hemicorporectomy (at the level between the lowest lumbar vertebra and the sacrum) was performed 18 months later by J. Bradley Aust and Karel B. Absolon, of Minnesota. This operation would never have been possible without all the technical, supportive, and rehabilitative resources of modern medicine.heart surgeryThe attitude of the medical profession toward heart surgery was for long overshadowed by doubt and disbelief. Wounds of the heart could be sutured (first done successfully by Ludwig Rehn, of Frankfurt am Main, in 1896); the pericardial cavity—the cavity formed by the sac enclosing the heart—could be drained in purulent infections (as had been done by Larrey in 1824); and the pericardium could be partially excised for constrictive pericarditis when it was inflamed and constricted the movement of the heart (this operation was performed by Rehn and Sauerbruch in 1913). But little beyond these procedures found acceptance.Yet, in the first two decades of the 20th century, much experimental work had been carried out, notably by the French surgeons Théodore Tuffier and Alexis Carrel. Tuffier, in 1912, operated successfully on the aortic valve. In 1923 Elliott Cutler of Boston used a tenotome, a tendon-cutting instrument, to relieve a girl's mitral stenosis (a narrowing of the mitral valve between the upper and lower chambers of the left side of the heart) and in 1925, in London, Henry Souttar used a finger to dilate a mitral valve in a manner that was 25 years ahead of its time. Despite these achievements, there was too much experimental failure, and heart disease (cardiovascular disease) remained a medical, rather than surgical, matter.Resistance began to crumble in 1938, when Robert Gross successfully tied off a persistent ductus arteriosus (a fetal blood vessel between the pulmonary artery and the aorta). It was finally swept aside in World War II by the remarkable record of Dwight Harken, who removed 134 missiles from the chest—13 in the heart chambers—without the loss of one patient.After the war, advances came rapidly, with the initial emphasis on the correction or amelioration of congenital defects. Gordon Murray, of Toronto, made full use of his amazing technical ingenuity to devise and perform many pioneering operations. And Charles Bailey of Philadelphia, adopting a more orthodox approach, was responsible for establishing numerous basic principles in the growing specialty.Until 1953, however, the techniques all had one great disadvantage: they were done “blind.” The surgeon's dream was to stop the heart so that he could see (open-heart surgery) what he was doing and be allowed more time in which to do it. In 1952 this dream began to come true when Floyd Lewis, of Minnesota, reduced the temperature (cryosurgery) of the body so as to lessen its need for oxygen while he closed a hole between the two upper heart chambers, the atria. The next year John Gibbon, Jr., of Philadelphia brought to fulfillment the research he had begun in 1937; he used his heart–lung machine to supply oxygen while he closed a hole in the septum between the atria.Unfortunately, neither method alone was ideal, but intensive research and development led, in the early 1960s, to their being combined as extracorporeal cooling. That is, the blood circulated through a machine outside the body, which cooled it (and, after the operation, warmed it); the cooled blood lowered the temperature of the whole body. With the heart dry and motionless, the surgeon operated on the coronary arteries; he inserted plastic patches over holes; he sometimes almost remodeled the inside of the heart. But when it came to replacing valves destroyed by disease, he was faced with a difficult choice between human tissue and man-made valves, or even valves from animal sources.Organ transplantationIn 1967 surgery arrived at a climax that made the whole world aware of its medicosurgical responsibilities when the South African surgeon Christiaan Barnard (Barnard, Christiaan) transplanted (transplant) the first human heart. Reaction, both medical and lay, contained more than an element of hysteria. Yet, in 1964, James Hardy, of the University of Mississippi, had transplanted a chimpanzee's heart into a man; and in that year two prominent research workers, Richard Lower and Norman E. Shumway, had written: “Perhaps the cardiac surgeon should pause while society becomes accustomed to resurrection of the mythological chimera.” Research had been remorselessly leading up to just such an operation ever since Charles Guthrie and Alexis Carrel (Carrel, Alexis), at the University of Chicago, perfected the suturing of blood vessels in 1905 and then carried out experiments in the transplantation of many organs, including the heart.New developments in immunosuppression (the use of drugs to prevent organ rejection) have advanced the field of transplantation enormously. Kidney transplantation is now a routine procedure that is supplemented by dialysis with an artificial kidney (invented by Willem Kolff in wartime Holland) before and after the operation; mortality has been reduced to about 10 percent per year. Rejection of the transplanted heart by the patient's immune system was overcome to some degree in the 1980s with the introduction of the immunosuppressant cyclosporine; records show that many patients have lived for five or more years after the transplant operation.The complexity of the liver and the unavailability of supplemental therapies such as the artificial kidney have contributed to the slow progress in liver transplantation (first performed in 1963 by Thomas Starzl). An increasing number of patients, especially children, have undergone successful transplantation; however, a substantial number may require retransplantation due to the failure of the first graft.Lung transplants (first performed by Hardy in 1963) are difficult procedures, and much progress is yet to be made in preventing rejection. A combined heart-lung transplant is still in the experimental stage, but it is being met with increasing success; two-thirds of those receiving transplants are surviving, although complications such as infection are still common. Transplantation of all or part of the pancreas is not completely successful, and further refinements of the procedures (first performed in 1966 by Richard Lillehei) are needed.Robert G. Richardson Ed.Additional ReadingThe literature on the history of medicine covers all topics and periods and includes biographies as well as descriptions of the development of hospitals, research institutes, health care, and medical education in different countries. Introductory studies include George T. Bettany, Eminent Doctors: Their Lives and Their Work, 2 vol. (1885, reprinted 1972); Arturo Castiglioni, A History of Medicine, 2nd rev. ed. (1947; originally published in Italian, 1927), a classic work; Fielding H. Garrison, An Introduction to the History of Medicine, 4th rev. ed. (1929, reprinted 1967), a scholarly history; Douglas Guthrie, A History of Medicine, rev. ed. (1958); Howard W. Haggard, Devils, Drugs, and Doctors: The Story of the Science of Healing from Medicine-Man to Doctor (1929, reprinted 1980); Richard H. Meade, An Introduction to the History of General Surgery (1968), a well-documented work on developments in surgery on separate organs; Charles Singer and E. Ashworth Underwood, A Short History of Medicine, 2nd ed. (1962); and Philip Rhodes, An Outline History of Medicine (1985). The Oxford Companion to Medicine, 2 vol., edited by John Walton, Paul B. Beeson, and Ronald Bodley Scott (1986), is a comprehensive text of 20th-century developments and persons.Ancient traditions of non-Western medicine are presented in P. Kutumbiah, Ancient Indian Medicine (1962); Heinrich R. Zimmer, Hindu Medicine (1948, reprinted 1979); Edward H. Hume, The Chinese Way in Medicine (1940, reprinted 1975); Paul U. Unschuld, Medicine in China: A History of Ideas (1985; originally published in German, 1980); and Edward G. Browne, Arabian Medicine (1921, reprinted 1983).For developments from the origin of Western medicine to the end of the 18th century, see William G. Black, Folk-Medicine: A Chapter in the History of Culture (1883, reprinted 1970); W.H.R. Rivers, Medicine, Magic, and Religion (1924, reprinted 1979), a comprehensive treatment of primitive medicine; John Scarborough, Roman Medicine (1969, reprinted 1976); Robert S. Gottfried, Doctors and Medicine in Medieval England, 1340–1530 (1986); A. Wear, R.K. French, and I.M. Lonie (eds.), The Medical Renaissance of the Sixteenth Century (1985); Katharine Park, Doctors and Medicine in Early Renaissance Florence (1985); and Guy Williams, The Age of Agony: The Art of Healing, c. 1700–1800 (1975, reprinted 1986).Medicine and surgery during the 19th and 20th centuries are the subject of Carl J. Pfeiffer, The Art and Practice of Western Medicine in the Early Nineteenth Century (1985); Thomas E. Keys, The History of Surgical Anesthesia, rev. ed. (1963, reprinted 1978); M.H. Armstrong Davison, The Evolution of Anesthesia (1965); Robert G. Richardson, The Scalpel and the Heart (1970; U.K. title, The Surgeon's Heart: A History of Cardiac Surgery, 1969); John S. Haller, Jr., American Medicine in Transition, 1840–1910 (1981); Ruth J. Abram (ed.), Send Us a Lady Physician: Women Doctors in America, 1835–1920 (1985); George Rosen, The Structure of American Medical Practice, 1875-1941 (1983); A. McGehee Harvey, Science at the Bedside: Clinical Research in American Medicine, 1905–1945 (1981), a discussion of the institutionalization of clinical research; and Lawrence Galton, Med Tech: The Layperson's Guide to Today's Medical Miracles (1985), a historical dictionary.
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