IELTS Academic Reading Practice Test 345

For well over a thousand years, a physician who never dissected a human brain or a human heart shaped what European and Islamic doctors believed about the body. Galen of Pergamon was born in AD 129 in the Greek city of Pergamon, in what is now western Turkey, and became the most prolific medical writer of antiquity. His ideas were still taught in universities in the seventeenth century, and his authority was so complete that for centuries to question him was close to heresy. Yet his anatomy was largely the anatomy of animals, and much of it was wrong.

Galen's father, Nicon, was a wealthy architect and landowner who gave his son an unusually broad education in philosophy, mathematics and literature. According to Galen's own account, a dream told his father to steer the boy towards medicine, and Galen began his medical studies at about the age of sixteen. He then travelled widely, studying in Smyrna and Corinth and finally at Alexandria in Egypt. Alexandria offered the best medical teaching of the age; two physicians of the third century BC, Herophilus and Erasistratus, are said to have dissected human bodies there, but by Galen's time the practice had long since fallen out of favour.

He returned to Pergamon at the age of twenty-eight and was appointed physician to the city's gladiators, a post arranged by the high priest. The work was dangerous and poorly paid, but it gave him something no textbook could: a steady supply of serious wounds. He later wrote that the injuries of the gladiators were windows through which he could observe the interior of a living body — muscles, tendons, bones and the membranes around organs. He became skilled at dressing wounds, and he noted with some pride that only two of the gladiators under his care had died, a strikingly low figure for the period.

In AD 162 Galen moved to Rome, then the largest city in the western world, and set about building a reputation. He gave public lectures and demonstrations, and his most celebrated performances involved the dissection of live animals. In one, he cut the nerves in the neck of a pig, first one and then the other, and showed that the animal's squealing stopped while it continued to breathe and move. In another, he tied off the tubes leading from the kidneys and demonstrated that urine collected above the knot rather than below it. Such experiments were intended to show that particular organs perform particular functions, and they made him famous and, among rival doctors, unpopular.

Because he could not dissect human bodies, Galen transferred what he found in animals to people, and the errors that resulted were repeated for more than a millennium. He described a delicate mesh of blood vessels beneath the brain, which he called the rete mirabile; it is found in oxen and other hoofed animals but not in humans. He gave the liver five lobes, as it has in dogs, and he held that blood seeped through the dividing wall of the heart by way of tiny pores that no one could see, an idea he reached by reasoning rather than by observation.

His account of how the body worked was, in its own terms, remarkably systematic. He proposed that the liver converted food into blood, which was carried by the veins and consumed by the tissues. The heart, he thought, produced a vital spirit that travelled through the arteries, while the brain produced an animal spirit which flowed along hollow nerves to produce movement and sensation. Health depended on the balance of four humours: blood, phlegm, yellow bile and black bile. This idea, inherited from earlier Greek thinkers, became in Galen's hands a complete system of diagnosis and treatment, including diet, exercise and bloodletting.

In AD 166 a severe epidemic — probably smallpox, though the identification is disputed — swept through the Roman Empire, and Galen left Rome for Pergamon. He was later recalled by the emperor Marcus Aurelius, who valued his learning, and he spent much of the rest of his life in imperial service, eventually becoming physician to Marcus's son Commodus. The year of his death is uncertain; the figure usually given is around AD 216.

Galen wrote enormously. His surviving works alone amount to nearly three million words, and many more are known to have been lost; what remains was copied by hand over centuries. The survival of even that fraction owes a great deal to later translators: his works were rendered into Syriac, Arabic and then Latin. Physicians in the medieval Islamic world, among them al-Razi, studied and commented on him. By the time printing reached Europe in the fifteenth century, the Galenic corpus was one of the largest bodies of ancient scientific writing in existence.

Correction came slowly. In 1543 the Flemish anatomist Andreas Vesalius, who had dissected human cadavers himself, published a detailed atlas of the human body. He pointed out, politely but firmly, a series of places where Galen had described animals rather than people. It took more than a century for the physiology to follow. When William Harvey showed in 1628 that blood circulates continuously around the body, driven by the heart, the Galenic scheme of ebbing and flowing was finally displaced. Galen's reputation nevertheless survives among historians of medicine, less for his conclusions than for his methods: he insisted on observation, on dissection and on testing ideas against what could actually be seen.

The pancreas is a soft, elongated organ about fifteen centimetres long that lies behind the stomach and partly beneath it. Most of its tissue — well over ninety per cent — is devoted to digestion: clusters of cells called acini produce enzymes that pass along a duct into the small intestine. Scattered through this digestive tissue are roughly a million tiny clumps, each less than half a millimetre across, which make hormones instead. In 1869 a German medical student, Paul Langerhans, described these clumps in his thesis without understanding what they did, and they were later named the islets of Langerhans in his honour.

The hormones themselves were identified only in the 1920s. In 1921 two researchers in Toronto, Frederick Banting and Charles Best, working in the laboratory of the physiologist John Macleod, produced an extract from the pancreas. The extract lowered blood sugar in dogs whose own pancreas had been removed. A biochemist, James Collip, then purified it enough to be given to people. In January 1922 a fourteen-year-old boy, Leonard Thompson, who was dying of diabetes, received the first injections; his condition improved dramatically, and insulin was being manufactured on a large scale within a few years.

Insulin is made by the beta cells, which make up the majority of the cells in an islet. They are unusual among cells in that they respond to a nutrient rather than to a signal from another cell. When blood glucose rises after a meal, glucose enters a beta cell through a transporter protein and is broken down, raising the level of ATP, the cell's energy currency. This closes channels in the cell membrane that normally allow potassium ions to escape, so the membrane becomes less negative inside. The change opens calcium channels, and the resulting flood of calcium triggers the release of insulin stored in small granules. The whole sequence takes only minutes.

Released into the blood that drains the islet, insulin travels first to the liver, where it signals that the body is in a fed state. It stimulates the liver to store glucose as glycogen and to stop manufacturing glucose from other molecules. It also prompts muscle and fat cells to move glucose transporters to their surface, so that sugar can be taken up from the blood, and encourages the storage of fat. The overall effect is to push the level of glucose in the blood back down. In type 1 diabetes the beta cells are destroyed by the immune system, and without injections the result is a life-threatening accumulation of glucose and acid in the blood.

On the other side of the balance are the alpha cells, which release glucagon when blood glucose falls. Glucagon acts mainly on the liver, where it promotes the breakdown of glycogen and the synthesis of new glucose from amino acids and other precursors. How alpha cells detect a fall in glucose is less clear than the equivalent mechanism in beta cells. A growing body of evidence, however, suggests that signals from neighbouring beta cells and from the delta cells that release somatostatin also help to keep them in check. The islet, in other words, behaves less like a collection of independent sensors than like a small organ that talks to itself.

A third layer of control comes from the gut. When food arrives in the intestine, cells in its lining release hormones called incretins, principally GLP-1 and GIP, which travel in the blood to the pancreas and amplify the release of insulin. The effect is considerable: the same amount of glucose given by mouth provokes a much larger insulin response than when it is infused directly into the blood. This difference between the two responses is known as the incretin effect. Incretins also slow the emptying of the stomach and increase the feeling of fullness. Two classes of drug now widely used in diabetes treatment exploit this system, one by mimicking GLP-1 and the other by blocking the enzyme that breaks it down.

The system fails in two main ways. In type 2 diabetes, which accounts for the great majority of cases, the tissues gradually stop responding to insulin, a condition known as insulin resistance. For years the beta cells can compensate by producing more insulin, and blood glucose may stay close to normal. Eventually, however, the cells cannot keep up, and glucose begins to accumulate in the blood. Why beta cells decline is still not fully understood. Deposits of a protein called amyloid are found in the islets of many people with the disease, and chronic low-grade inflammation is thought to contribute. According to the World Health Organization, the number of people with diabetes rose from 108 million in 1980 to 422 million in 2014.

Treatment has changed less than the understanding. People with type 1 diabetes still depend on injections or pumps that deliver insulin under the skin, and matching the dose to meals and exercise remains difficult; too much insulin causes dangerous hypoglycaemia. For decades the most promising alternative has been to replace the beta cells themselves. In 2000 a group in Edmonton, Canada, reported that islets taken from deceased donors and infused into the liver could free some patients with severe type 1 diabetes from injections. The effect required powerful drugs to suppress the immune system, however, and rarely lasted more than a few years. More recently, several groups have grown beta-like cells from stem cells and begun early trials in patients. Whether such cells will work at scale is not yet known.

Suppose a patient with a disease that will certainly kill them within a year learns of a compound that has been tested for safety in a few dozen healthy volunteers. Laboratory studies have shown some sign of activity against their condition. It has never been proved to help anyone. The company that owns it is running a trial, but the patient does not qualify. Should they be allowed to take it anyway? In the United States, and increasingly in other countries, the answer has been a qualified yes, through laws that grant terminally ill patients a right to try drugs that regulators have not approved. Whether those laws help patients, or merely make legislators feel better, is another matter.

The argument for such laws rests on autonomy, and on the peculiar position of the dying. A patient who will not survive the usual ten to fifteen years of drug development has no realistic prospect of benefiting from it; for them, the ordinary balance between risk and caution looks different. A treatment that has passed the first stage of testing, in which doses are established and obvious dangers identified, is not wholly unknown. The reasoning goes that an adult of sound mind should be free to weigh its remaining risks against the certainty of death. Advocates also point to the 1980s, when people dying of AIDS campaigned for access to experimental antivirals and helped to create a faster, more flexible approval system.

The laws that emerged from this debate, however, are not quite what that argument describes. Between 2014, when Colorado passed the first of them, and 2018, more than thirty American states adopted right-to-try statutes. In May 2018 a federal law was signed that allows patients with a life-threatening illness to request an unapproved drug directly from its manufacturer. The federal law requires only that the drug have completed a phase 1 safety trial, that the patient have considered approved alternatives, and that a doctor certify the request. Crucially, it removes the Food and Drug Administration from the process, and it obliges no company to supply the drug or to report what happens afterwards.

Opponents do not dispute the compassion behind such laws; they dispute the arithmetic. A drug that has completed a phase 1 trial has usually been given to fewer than a hundred people, often for a few weeks. It has been chosen for further study precisely because its benefits are unproven. Some experimental compounds turn out to cause serious harm that no small trial could have detected, and others interact dangerously with the medicines a patient is already taking. The risks are not hypothetical: many treatments that seemed harmless in small studies have proved harmful later.

Two further costs are less visible. The first is to the evidence itself. A drug given to patients outside a trial, without measurements or a comparison group, produces no reliable information about whether it works. The very patients who might have advanced knowledge are lost to it. The second is to trials: if a patient can obtain an experimental medicine without enrolling in a study, some will do so, and the trial that would have settled the question may recruit too slowly. Defenders reply that such fears are theoretical, since the number of patients who have used these laws is tiny — a fact that suggests the laws may not be the answer to a pressing problem.

It is also worth asking why new laws were needed at all. Since the 1980s the Food and Drug Administration has operated an expanded-access, or compassionate-use, programme that allows doctors to request unapproved medicines for individual patients. Applications are reviewed quickly, sometimes within days, and the agency says it approves the overwhelming majority of them. The programme covers more treatments than the new laws do, because it is not limited to patients near death, and it collects data on outcomes. Its weakness is bureaucracy: the forms are long, the process can take up a good deal of a doctor's time, and the drug company must agree to take part.

There remains the subtler question of how such choices are made. People facing death are not choosing in the conditions that economists assume. They are frightened, often in pain, and inclined to overestimate the chance of benefit and underestimate the chance of harm. Researchers describe a related confusion, in which patients assume that an experimental drug is being given mainly for their own benefit, as therapeutic misconception. That is an argument not for removing the choice but for structuring it: independent counselling, a clear statement of what is and is not known, and a requirement that the drug be provided free. The cost matters too. Some manufacturers charge for expanded-access drugs, and insurers may refuse to pay for an unapproved treatment, so access can end up depending on wealth.

Where does that leave the question? I would not deny a dying patient a medicine that has passed a safety trial and that a doctor is willing to supervise; the claim of autonomy is real, and the alternative is sometimes nothing at all. But the right-to-try laws passed in the United States do not mainly provide access. They provide a political gesture that removes regulatory oversight and data collection while leaving the decision to supply the drug in the hands of the manufacturer, which is why so few patients have benefited. A better approach would keep the oversight, speed up the paperwork, require companies to report outcomes and, where possible, allow the treatment to be given within a trial.