You should spend about 20 minutes on Questions 1–13, which are based on Reading Passage 1 below.
The Discovery of Insulin
Before the 1920s, a diagnosis of diabetes in a child was effectively a death sentence. The disease, in which the body cannot regulate the sugar in its blood, had been described since ancient times, but no treatment could keep a young patient alive for long. The American physician Frederick Allen had shown that severe restriction of food could prolong life, and his regime of controlled undernutrition became the standard approach. Children were kept on the edge of starvation for months or years, thin and weak, while their families waited for something better to appear.
The idea that the pancreas held the key was not new. In 1889 Oscar Minkowski and Josef von Mering removed the pancreas from dogs and found that the animals developed the symptoms of diabetes, establishing that the organ produced something the body needed. In 1920 a young Canadian surgeon called Frederick Banting, practising orthopaedics in London, Ontario, read an article by Moses Barron describing how, if the duct leading from the pancreas was tied off, the tissue producing digestive juices wasted away while small clusters of cells — the islets of Langerhans — survived. Banting's idea was to tie off the duct, wait for the rest of the organ to degenerate, and extract whatever the surviving islets produced.
Banting had no research experience and little equipment. He took his proposal to John Macleod, a respected physiologist at the University of Toronto, who was doubtful but eventually gave him a laboratory for eight weeks in the summer of 1921, together with a medical student, Charles Best, who knew how to carry out the necessary blood and urine tests. The work began badly. Dogs died after surgery and the heat made the small laboratory unbearable.
By the end of that summer they had something that worked, at least in dogs. An extract of pancreas, injected into an animal whose own pancreas had been removed, lowered the sugar in its blood and urine and restored some of its strength. The results were rough and inconsistent, but the principle was established: the missing factor could be extracted from pancreatic tissue and injected. Macleod now put the resources of his department behind the work and asked a trained biochemist, James Collip, then on leave from the University of Alberta, to join the team.
Collip's contribution proved decisive. The extract Banting and Best had produced was crude and caused fever and abscesses when injected; making it pure enough for human use required chemical skills that the two original researchers did not have. Working through the winter, Collip developed a method of extracting the hormone with alcohol and then removing the impurities, and by early 1922 he had a preparation that could be given to patients. The collaboration was tense, and the four men quarrelled repeatedly.
The first attempt on a human being was made in January 1922 at Toronto General Hospital. Leonard Thompson, a teenage boy who was close to death, received an injection of the Toronto extract, which had little effect on his blood sugar and caused painful swelling at the site. Collip's purified material was used for a second attempt on 23 January. This time the boy's blood sugar fell sharply, sugar disappeared from his urine, and his condition improved. He survived for another thirteen years.
News travelled fast. In August 1922 Elizabeth Hughes, the teenage daughter of the American statesman Charles Evans Hughes, arrived in the city after years on a strict starvation diet; she was treated by Banting, recovered sufficiently to return to school, and lived into her seventies. Her case, reported in newspapers, did as much as any scientific paper to convince the public that a genuine treatment had been found. Doctors came from Europe to learn the technique.
Supplying enough extract was the next problem. The pancreas of a single animal yields only a small quantity of hormone, and thousands of animals were needed. The team at Connaught Laboratories, part of the university, worked on standardising the strength of the extract so that doses could be measured reliably, and production was licensed to pharmaceutical companies. In 1923 the patent was sold to the university for the nominal sum of one dollar, a decision intended to stop any single firm from controlling the supply. Insulin was soon manufactured in several countries.
In 1923 the Nobel Prize in Physiology or Medicine was awarded to Banting and Macleod. The choice was controversial, since Best and Collip had been left out, and Banting, angry on Best's behalf, at first considered refusing the prize. He eventually shared his share of the money with Best, and Macleod shared his with Collip. The argument over who deserved what continued for the rest of their lives. Banting, who was knighted in 1934, was killed in an air crash in Newfoundland in 1941 while travelling on war work.
Insulin turned diabetes from a terminal illness into a condition that could be managed, though it was never a cure, and injections had to be repeated for life. For more than half a century the hormone was extracted from the pancreases of cattle and pigs. In 1982, after years of research into genetic engineering, a form of human insulin produced by bacteria was approved for use. Yet the underlying problem identified in Toronto a century ago, that the body has lost cells it cannot replace, remains a subject of research today.
You should spend about 20 minutes on Questions 14–26, which are based on Reading Passage 2 below.
Why We Develop a Fever
A rise in body temperature is one of the oldest and least specific signs of illness. The familiar figure of 37°C as the normal temperature comes from Carl Wunderlich, a German physician who in the middle of the nineteenth century compiled readings from thousands of patients in Leipzig and calculated an average. Modern measurements suggest that his figure is slightly too high: an analysis of American adults published in 2017 put the mean closer to 36.6°C. Temperature also falls in the early morning and rises towards evening, and it differs between individuals by a few tenths of a degree.
Fever is not simply a body that has become hot. Deep in the brain, a region called the hypothalamus acts as a thermostat, adjusting heat production and heat loss to hold the core temperature near a set point. In hyperthermia — heat stroke, or collapse during extreme exercise — the set point is unchanged, but heat is gained faster than it can be lost, and drugs given for fever have no effect. A fever is different: the set point itself is raised, and the body then works to reach the new target.
The chain of events begins when cells of the immune system encounter fragments of bacteria or viruses. These cells release small proteins known as cytokines, including interleukin-1 and interleukin-6, which travel in the blood and act on the hypothalamus. Fever can also appear in conditions that involve no infection at all, such as some inflammatory diseases and cancers, because the same messengers are released by damaged tissue. Because the messengers are shared, a fever shows that the body is responding to something, but not what that something is.
At the hypothalamus the decisive step is the manufacture of prostaglandin E2. An enzyme called cyclo-oxygenase converts a fatty acid into this short-lived messenger, which alters the activity of the neurons controlling heat loss and heat production. Aspirin and ibuprofen relieve fever by blocking this enzyme, which is also why they ease pain and inflammation at the same time; paracetamol acts on the same system in the brain, although its precise mechanism is still debated.
Once the set point has risen, a person feels cold and behaves accordingly, putting on extra clothes or curling up under a blanket. Blood vessels near the surface of the skin narrow, so that less heat is lost, and the muscles begin to shiver, generating heat through rapid contraction. When the infection passes and the set point returns to normal, the body has more heat than it needs, and sweating and flushing remove the surplus.
Why should the body do this? The older view, that fever is a dangerous malfunction to be suppressed as quickly as possible, has been challenged by a growing body of evidence that the rise in temperature is part of the defence. Many bacteria and viruses multiply most efficiently at the temperature of a healthy body and less efficiently when it rises, and some immune reactions proceed faster in the warm. The body also withdraws iron from the blood during infection, and since many microbes need iron in order to grow, this deprives them of an essential nutrient.
Animal evidence supports the idea. Fish, lizards and other cold-blooded animals infected with bacteria move to warmer places, and those that do so often survive better than those prevented from doing it. In humans the picture is less clear. Trials in which patients were given drugs to suppress fever have produced mixed results, some suggesting a slightly longer illness and others finding no difference, and the studies are generally small.
Whatever its purpose, a fever is expensive for the body. Each degree of extra temperature increases the heart rate and the consumption of oxygen, which is why a fever is more worrying in someone whose heart or lungs are already strained, and why it can leave a patient dehydrated. In a small minority of young children, between about six months and five years of age, a rapid rise in temperature triggers a convulsion; frightening as these are, they rarely cause lasting harm. Fever caused by infection seldom climbs above about 41°C.
Measurement is less precise than it appears. A thermometer in the mouth, the ear or the armpit gives a different reading in each case, and none of them measures the temperature of the core directly. Current guidance generally advises treating the patient's discomfort rather than the number on the display, and it is worth remembering that a drug lowers the temperature without touching the infection that caused it.
Fever also has a pattern, and doctors once read a great deal from it. A temperature that swings widely within a day suggests a different cause from one that stays steadily high. Modern tests have made such readings less central than they once were, but the thermometer remains one of the cheapest diagnostic instruments available.
You should spend about 20 minutes on Questions 27–40, which are based on Reading Passage 3 below.
Should the State Pay for Complementary Medicine?
The argument over public funding for therapies outside conventional medicine
Health systems everywhere face the same arithmetic: demands rise and budgets do not. In that climate a question that once seemed marginal has become urgent. Should public money pay for treatments that sit outside conventional medicine? Acupuncture, homeopathy, herbal preparations and manipulative therapies are used by large numbers of people, most of whom pay for them themselves, and private spending on such treatments is substantial. Whether the state should pick up the bill is often discussed as a matter of taste or tradition. It is, or ought to be, a question about evidence, fairness and the proper use of scarce funds.
The strongest argument for funding is not that these therapies work but that access to them is unequal. A patient who can afford private sessions can try acupuncture for chronic back pain; a patient on a low income cannot. Supporters also argue that several therapies cost less per session than some conventional treatments, so that refusing to pay does not save money so much as reserve the option for those who already have it. Others appeal to tradition, maintaining that a practice which has survived for centuries is unlikely to be entirely worthless. Practitioners, meanwhile, typically spend longer with patients than a crowded clinic allows, and patients value that time. The sums at stake are small beside the cost of a hospital, but they are not trivial for a family on a low income.
Nor is the cupboard bare. Some therapies have moved from the fringe towards the mainstream because trials supported them. A large pooled analysis of individual patient data found that acupuncture performed better than both sham needling and usual care for several chronic pain conditions, although the differences were modest. Herbal medicine has supplied conventional drugs: aspirin was developed from a compound found in willow bark, and digoxin, used in heart failure, comes from the foxglove. For a funding body the relevant question is not whether a therapy is old or unfamiliar but whether it does more good than the alternatives for the money it costs.
The case against public funding rests on a smaller number of examples that are, unfortunately, extremely expensive. Homeopathy is the clearest. Its remedies are diluted to the point at which, on the principles of chemistry, no molecule of the original substance is likely to remain, and no mechanism has been demonstrated by which such a preparation could act. A review commissioned by Australia's National Health and Medical Research Council concluded in 2015 that there were no health conditions for which reliable evidence showed homeopathy to be effective. Paying for it is not a neutral act: it lends the authority of the state to a form of medicine that has not been shown to work.
Supporters sometimes reply that if patients feel better, the mechanism hardly matters, and that conventional doctors prescribe placebos too. The reply is superficially attractive and ultimately unconvincing. A placebo may relieve a symptom, but a health system that funds an entire theory of illness on the strength of that effect is paying for a claim it cannot defend, and it does so with money that could buy something with a demonstrated benefit.
Safety is a separate matter, and a more serious one. Complementary therapies are often assumed to be harmless because they are natural, yet herbal preparations contain active compounds that can interact with prescribed drugs. St John's wort, widely taken for low mood, is known to speed the breakdown of several medicines, including drugs used after organ transplantation and some contraceptives. There is also indirect harm when a treatable disease goes untreated because a patient has been reassured by a practitioner who did not recognise its seriousness. Regulation of both practitioners and products varies widely between countries, and where it is weak the risks fall on those least able to check credentials.
What would a defensible policy look like? It would fund treatments that have been shown in adequate trials to help patients, and decline to fund those that have not, applying the same standard it applies to drugs and surgery. It would pay for research where the evidence is missing but the therapy is plausible, since an absence of evidence is often the result of nobody having paid for the studies. It would regulate practitioners, require honest labelling of products, insist that therapists refer patients on when a condition needs conventional care, and be honest with the public about what it is buying.
Critics of this position raise an obvious objection: conventional medicine contains plenty of practices that have never been tested in a satisfactory trial, and they are funded without controversy. That is true, and it is a reason to test them rather than a reason to abandon the standard. The asymmetry lies elsewhere. Conventional treatments are at least expected to demonstrate benefit, whereas some complementary ones rest on theories that could not be tested even in principle.
My own view, then, is neither a blanket refusal nor an open door. Public funding should follow evidence, and where the evidence is thin it should buy the research that would produce some. What it should not do is purchase a comforting parallel system whose central claims have failed every serious examination. Patients deserve choice, but choice is worth little if the options on offer are not honestly described. That is a modest conclusion, and it will satisfy neither those who want these therapies celebrated nor those who want them banned, but it is defensible.
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