You should spend about 20 minutes on Questions 1–13, which are based on Reading Passage 1 below.
The Birth of the Blood Bank
Blood transfusion is now so routine that few patients give it a thought, yet the technique took more than three centuries to become safe. The idea of moving blood from one body to another was first tested in the seventeenth century, when physicians in England and France experimented with animals. In 1667 the French physician Jean-Baptiste Denys transferred blood from a sheep into a young man and reported a favourable outcome, and several similar attempts followed. Other patients were less fortunate. After a series of deaths the practice was restricted in France and then abandoned, and transfusion fell out of use for around 150 years.
The revival came in the nineteenth century and was driven by childbirth. Heavy bleeding after delivery was a common cause of death. The London obstetrician James Blundell, who worked at Guy's Hospital, became convinced that replacing the lost blood offered the only hope in the most desperate cases. He performed his first transfusion of human blood in 1818, using a syringe of his own design, and in 1829 he reported a mother who survived severe bleeding after being given blood. Blundell understood that animal blood was unsuitable and preferred human donors, often the husband of the patient. Yet the blood frequently clotted inside his apparatus, and many of those he treated died.
The reason so many transfusions failed remained invisible until 1901. In Vienna that year, Karl Landsteiner mixed samples of blood serum and red cells from himself and his colleagues, and noticed that some combinations clumped together. He concluded that human blood falls into distinct groups, which he labelled A, B and C; the third later became known as O. A fourth and rarer group, AB, was identified by other researchers within a year or two. The discovery explained why a transfusion from an incompatible donor could be fatal: the recipient's antibodies attack the unfamiliar red cells, which clump and may block the circulation. The work brought Landsteiner a Nobel Prize in 1930.
Even when donor and recipient were compatible, blood clotted within minutes once it left the body, so the two had to be connected by a tube and the operation performed at once. The solution came in 1914 and 1915, when researchers in Belgium, Argentina and the United States independently found that adding a little sodium citrate stopped blood from clotting by binding its calcium. Citrate made it possible to collect blood into a container, keep it for a time and carry it to the patient, instead of requiring the donor to be present. This practice of indirect transfusion was the essential step towards storage.
The First World War provided the first large-scale test. Oswald Hope Robertson, a young American medical officer serving with the British Army, experimented with a solution of citrate and glucose that allowed blood to be kept for longer. In 1917 he set up a depot of stored blood near the front line in France, in preparation for the battle of Cambrai. Wounded soldiers could therefore be given blood within minutes of reaching a casualty clearing station. Robertson's depot is often described as the first blood bank.
Twenty years passed before stored blood became a permanent feature of civilian medicine. The decisive figure was Bernard Fantus, a physician at Cook County Hospital in Chicago, who in 1937 opened a department that collected blood from donors, established each donation's group and kept it refrigerated. It was available to any doctor in the hospital who needed it. Fantus coined the term 'blood bank', borrowing the language of finance to convey deposits and withdrawals. Within two years similar banks had opened in several American cities and in Britain, and the cross-matching of donor and recipient blood had become a standard laboratory procedure.
Danger still lurked in a factor that Landsteiner himself helped to uncover. In 1940 he and Alexander Wiener described another antigen, first detected with the help of blood from rhesus monkeys and carried by most people, which could also provoke a reaction; it became known as the Rh factor. Its importance lay less in transfusion than in pregnancy. A mother who lacked the factor could become sensitised to blood from an Rh-positive fetus, with consequences for later pregnancies that were eventually prevented by injections of antibodies. Routine testing of donors and of pregnant women removed a large share of the remaining danger.
The Second World War transformed the scale of the operation. Researchers on both sides of the Atlantic developed an acid-citrate-dextrose solution that kept red cells viable for several weeks rather than days. Blood could therefore be collected in one place and shipped over long distances. Large civilian donor panels were organised, and plasma was separated from red cells so that each could be used for a different purpose. By 1945 the collection, testing, storage and distribution of blood had become an organised process run by national bodies rather than a bedside experiment.
After 1945 the technology continued to improve. Disposable plastic bags, introduced in the 1950s, replaced glass bottles, and a single donation could be divided into red cells, plasma and platelets for different patients. Screening for infection, from syphilis to hepatitis and later HIV, became routine, and shortages remain because blood cannot be manufactured and keeps for only a few weeks. Every modern transfusion still rests on a chain of discoveries that began with a sheep in Paris.
You should spend about 20 minutes on Questions 14–26, which are based on Reading Passage 2 below.
The Machinery of Reward
In 1954 two young researchers at McGill University in Montreal, James Olds and Peter Milner, implanted fine electrodes in the brains of rats. The animals could press a lever to deliver a small electrical current. In certain positions the rats pressed the lever thousands of times an hour, sometimes neglecting food and water, and would cross an electrified grid to reach it. The result, as the two men later described it, owed something to chance: they had intended to study a quite different part of the brain. Their finding suggested that the brain contains structures devoted to reward, and a field of research was born.
The anatomy of that system has since been mapped in some detail. The central players are neurons that produce dopamine, a chemical messenger manufactured in a small region of the midbrain called the ventral tegmental area. These neurons send long projections to the nucleus accumbens, a structure deep in the front of the brain, and to the prefrontal cortex and the amygdala. Dopamine is not the only substance involved: natural opioids, endocannabinoids and the amino acid glutamate all influence the circuit. The word 'system' is therefore slightly misleading, since what exists is a set of overlapping networks rather than a single pathway.
For decades dopamine was known to the public as the brain's pleasure chemical. The experiments that changed how scientists think about it were carried out in the 1990s by Wolfram Schultz. Schultz recorded individual dopamine neurons in monkeys as they learned to associate a signal with a drop of fruit juice. When the juice arrived unexpectedly, the neurons fired vigorously. After the animals had learned the association, the same neurons responded to the signal that predicted the juice rather than to the juice itself. When an expected reward failed to arrive, their activity fell below its resting level. In other words, the neurons seemed to signal the difference between the reward that was expected and the reward that arrived.
Such results implied that dopamine is less concerned with pleasure than with prediction, a conclusion reinforced by the work of Kent Berridge and his colleagues at the University of Michigan. Berridge distinguishes 'wanting' from 'liking'. Liking, the simple pleasure of a sweet taste for example, is produced in small 'hotspots' within the nucleus accumbens and a neighbouring region, the ventral pallidum. Wanting, by contrast, is the motivation to pursue something, and it depends on dopamine. Rats whose dopamine has been removed still show the facial expressions associated with sweet tastes, yet make no effort to obtain sugar. Berridge argues that the two experiences depend on different chemical systems, and that dopamine belongs to the machinery of pursuit rather than enjoyment.
If dopamine is a signal for learning rather than a fountain of pleasure, why do addictive drugs feel so compelling? Drugs such as cocaine and amphetamines raise dopamine concentrations in the nucleus accumbens far above the levels produced by food or conversation. They also do so in a way that is not linked to any useful prediction. Repeated use appears to make the brain more responsive to the cues associated with a drug and less responsive to the drug itself, so that the pursuit becomes more urgent as the pleasure fades. Brain scans by Nora Volkow and her colleagues have found fewer dopamine receptors of one type in people with addiction than in people without it. Whether this is a cause or a consequence of repeated drug use remains disputed.
Researchers have several ways of watching the system at work, each with a different question and its own blind spots. The most familiar is functional magnetic resonance imaging, which shows which parts of the brain use more oxygen while a person performs a task. Its weakness is that the signal reflects changes in blood flow, not electrical activity in neurons directly, and that it averages the activity of millions of cells. In animals, electrodes can record from a single neuron, which gives precision but requires the animal to be still and the task to be simple. Positron emission tomography can show how many receptors of a given kind are present, while genetic techniques allow particular cells in rodents to be switched on or off.
Many questions remain open. The most basic is what dopamine actually encodes. Some researchers hold that it reports a prediction error, as Schultz's work suggests. Others argue that it signals the salience of a stimulus, that is, how much attention it deserves, whether or not it is welcome. A third view links it to the vigour with which an animal pursues any goal. These accounts are not always easy to separate in experiments, and all of them rest heavily on work with rodents and monkeys. Whether the same circuits behave in the same way in people is difficult to establish, and the answer may vary between individuals.
The practical consequences reach well beyond the laboratory. Drugs that boost dopamine, prescribed for Parkinson's disease, can trigger compulsive gambling in a minority of patients, a reminder that the system does not distinguish between a legitimate goal and a harmful one. Antipsychotic medicines work by blocking dopamine receptors, which helps to control hallucinations but may also flatten motivation. The fashionable notion that a person can 'detox' from dopamine has little to support it, since dopamine is essential for movement as well as for motivation and cannot be removed at will. What the research does suggest is that environments offering easy access to powerful rewards deserve careful regulation.
You should spend about 20 minutes on Questions 27–40, which are based on Reading Passage 3 below.
Should Cycle Helmets Be Compulsory?
The evidence behind a familiar safety law is less clear-cut than it appears
Few laws seem as obviously sensible as the requirement to wear a helmet on a bicycle. A helmet is a shell of rigid foam that crushes on impact, spreading the force of a blow over a wider area. A cyclist who falls without one may suffer injuries from which there is no recovery. Yet the question of whether the state should compel every rider to wear one has divided researchers, cycling organisations and governments for more than thirty years. The argument turns on evidence that is far less tidy than the simple image of a cracked helmet suggests.
The strongest evidence for helmets comes from studies of injured cyclists arriving at hospitals. The best known, published in 1989 by a team in Seattle, compared riders treated for head injuries with riders treated for other injuries. It concluded that those wearing helmets had a much lower risk of head injury, a reduction often quoted as 85 per cent. Later studies in several countries have generally found lower risks of severe head injury among helmet wearers. The physical principle is not in doubt: a layer of foam can absorb energy that would otherwise be delivered to the brain. On this view, a law is merely a way of ensuring that people do something that is plainly in their own interest.
Critics, however, argue that this body of work cannot bear the weight placed on it. In the Seattle study and others like it, the comparison group consisted of cyclists who had also been injured. That makes it hard to know what would have happened to helmet wearers had they not been wearing helmets. Riders who choose to wear a helmet may differ from those who do not in ways that matter: they may be more cautious, less experienced, or riding in different places and at different speeds. Several analyses have found that helmeted riders tend to be involved in different kinds of crash, and a statistical association observed in an emergency department is a weak foundation for a national law.
Population figures are equally difficult to interpret. Australian states introduced compulsory helmets in the early 1990s, and New Zealand followed in 1994. Hospital admissions for cycling head injuries fell after the laws came into force, which supporters regard as decisive. Opponents reply that the number of people cycling also fell, in some places sharply. If fewer cyclists ride, they argue, the risk per hour of cycling may barely have changed, and the law may have delivered little benefit while removing a healthy activity from the streets. Neither side can point to an experiment, because no government has removed a helmet law in order to test the consequences.
The arithmetic of risk and benefit is often ignored. The health gains from regular cycling are substantial: physical inactivity is a major contributor to heart disease, diabetes and some cancers. Riders who replace car journeys with bicycle journeys gain considerably more in life expectancy than they lose in crash risk. If a law deters even a small proportion of people from cycling, the resulting harm to public health could outweigh the head injuries prevented. The danger of cycling also depends heavily on how many people do it. In the Netherlands and Denmark, where helmet use is low and cycling is common, death rates per kilometre cycled are among the lowest in the world. The pattern is usually explained by better infrastructure and by drivers who are used to sharing the road.
It is also worth being precise about what a helmet can and cannot do. It protects the skull and reduces the severity of direct impacts, particularly at the speeds typical of a fall from a bicycle. It is much less effective against the rotational forces that are thought to cause concussion, and no helmet prevents a rider from being struck by a lorry. Promoters of cycling argue, too, that a focus on helmets distracts attention from the measures that would prevent crashes in the first place, such as separated lanes, lower speed limits in residential streets and better lighting at junctions.
Enforcement raises further objections. A law enforced by fines falls most heavily on those least able to pay, and in some cities police stops for helmet offences have been concentrated in poorer neighbourhoods. Children are affected disproportionately, since parents may decide that a street where helmets are compulsory is too troublesome for a short journey to school. There is a symbolic cost as well. Making a helmet mandatory implies that cycling is a dangerous activity requiring protective equipment, which may discourage exactly the people who would benefit most from the exercise. In practice such laws are often enforced leniently.
My own view is that a compulsory helmet law for adults cannot be justified by the evidence now available. The protection offered is real but modest, the population data are ambiguous, and the risk of discouraging exercise is serious in countries where most adults take far too little. For children the case is stronger, because their crashes are more often simple falls and because a habit formed young may persist; even there, a law without safe routes to school achieves little. The first duty of a government is to make cycling safe, not to require its citizens to dress for danger. Where helmets are compulsory, the rule should be accompanied by sustained investment in protected infrastructure and should never be used as a substitute for it.
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