You should spend about 20 minutes on Questions 1–13, which are based on Reading Passage 1 below.
The Anatomy of the Brain: Thomas Willis
Thomas Willis was born in 1621 at Great Bedwyn in Wiltshire, the eldest son of a farmer. At sixteen he entered Christ Church, Oxford, and might have become a country clergyman had the civil war not interrupted his plans. He turned instead to medicine, taking his degree in 1646, and stayed in Oxford for the next twenty years. The town was the headquarters of the royalist cause, and Willis, a loyal supporter of the king, found no shortage of patients among the gentry and among wounded soldiers. Medicine at the time still rested largely on the writings of the ancient Greeks, and the workings of the brain were explained in terms of spirits flowing through its hollow cavities.
In Oxford he gathered around him a group of young men who shared his interest in experiment. They met in his lodgings, first in Beam Hall, to dissect animals and discuss what they found. Among them were Robert Hooke, later famous for his work with microscopes, Christopher Wren, who would design St Paul's Cathedral, and the chemist Robert Boyle. When Charles II granted a charter to the Royal Society in 1662, several of these men were among its early members, and the Oxford group has often been described as one of the roots from which that society grew.
In 1664 Willis published Cerebri Anatome, a Latin title that translates as 'the anatomy of the brain'. It was the most thorough account of the nervous system yet written and remained a standard work for two centuries. He dissected the brains of many kinds of animal and set them beside human specimens, looking for differences that might explain the mental powers people possess and other creatures seemingly do not. Much of the book's value lay in its illustrations: Wren, an accomplished draughtsman as well as an architect, drew the plates himself, and his pictures of the base of the brain are still admired. With his colleague Richard Lower, Willis also injected coloured liquids into blood vessels, a technique that made it possible to follow the course of an artery deep inside an organ.
His most enduring discovery concerned the blood supply of the brain. At its base, branches of the two internal carotid arteries and the two vertebral arteries join in a ring, so that if one vessel is narrowed or blocked, blood can still reach the tissue by another route. Willis described this arrangement in detail and had it clearly drawn; later anatomists called it the circle of Willis, and the name has stuck. The ring does not make the brain invulnerable — a blockage can still cause a stroke — but it provides a measure of protection that most other organs lack.
Willis was also a theorist. He rejected the long-established view that the mental faculties were housed in the fluid-filled cavities, or ventricles, at the centre of the brain. Instead he assigned different functions to different regions of solid tissue, placing memory and will in the folded outer layer, or cortex, and sensation and movement in the corpus striatum beneath it. The cerebellum, at the back of the skull, he linked to involuntary actions such as heartbeat and breathing, which continue without conscious control. Modern science has shown that most of this map is wrong, yet the attempt mattered: Willis treated the brain as a machine whose parts could be studied one by one, rather than as a single mysterious whole.
The book also gave the world a word. He needed a term for the study of the nerves and their disorders, and in Cerebri Anatome he used the Latin neurologia; from this the English word 'neurology' derives. He was less successful with the soul. In De Anima Brutorum, published in 1672, he argued that animals possess a material soul that perishes with the body, a position that unsettled some of his contemporaries.
In 1667 Willis left Oxford for London. There he built up one of the largest practices in the country, attending noblemen, merchants and clergy alike. Contemporaries described him as short, stout and quick-tempered, a man who worked long hours and expected his assistants to do the same. His casebooks record hundreds of patients suffering from headaches, dizziness, convulsions and paralysis, and it is on these careful records, as much as on his theories, that his reputation rests.
One of his most quoted observations concerns diabetes, a condition in which the body produces excessive urine. Greek and Arab physicians had described the disease centuries earlier, and its name, which means 'siphon', goes back to them. Willis, writing in 1674, added a detail that they had missed: he recorded that the urine of a diabetic patient tasted as though it had been sweetened with honey or sugar. The observation was accurate, and the sweet taste later gave the disease its full name, diabetes mellitus, mellitus being the Latin for honey-sweet. Why the sugar appeared, however, remained a mystery for another two hundred years.
Willis died in London in November 1675, aged fifty-four, and was buried in Westminster Abbey, where his monument can still be seen. He had hoped to be remembered not for any single discovery but for having opened the brain to systematic study, and in that ambition, at least, he succeeded.
You should spend about 20 minutes on Questions 14–26, which are based on Reading Passage 2 below.
The Blood-Brain Barrier
How the brain keeps the bloodstream at a distance — and why that makes brain disease so hard to treat
The human brain is protected from the rest of the body by a barrier that is remarkably effective. The walls of its capillaries are formed by a single layer of endothelial cells, the same kind of cell that lines blood vessels elsewhere, but here the cells are packed tightly together and surrounded by a thick basal lamina. Wrapped around them are the endfeet of astrocytes, a type of support cell, and the whole structure is reinforced by contractile cells called pericytes. The result is a filter that admits oxygen, water and glucose while excluding most toxins, microbes and large molecules, and that keeps the chemical environment of the brain stable enough for nerve cells to signal reliably.
The existence of such a barrier was suspected long before anyone could see it. In the 1880s the German physician Paul Ehrlich injected dyes into laboratory animals and found, to his surprise, that every organ was stained except the brain and spinal cord. Ehrlich assumed that the brain simply had no affinity for the dye. His student Edwin Goldmann later reversed the experiment, injecting dye into the cerebrospinal fluid that bathes the nervous system, and found exactly the opposite pattern: the brain was stained and the rest of the body was not. Between them, the two experiments suggested that something separates the blood from the tissue of the brain.
The idea was given a name in 1921 by Lina Stern, a physiologist working in Geneva with Raymond Gautier. Stern argued that the barrier was not a passive wall but an active interface, a system of membranes that selected what might pass and in what quantity. Her interpretation was largely neglected for decades, partly because she later moved to the Soviet Union, and partly because the tools needed to test it did not yet exist.
Proof came with the electron microscope. In 1967 Thomas Reese and Morris Karnovsky injected an enzyme called horseradish peroxidase into the blood of mice and then examined the brain capillaries under a microscope. The tracer travelled along the narrow gaps between the endothelial cells until it reached a point where the membranes of neighbouring cells appeared to fuse, and there it stopped. These seals, known as tight junctions, are the physical core of the barrier. They are not confined to the brain — similar junctions hold together the cells that line the gut and the skin — but only in the brain's capillaries are they continuous and exceptionally tight.
Crossing the barrier is therefore not a matter of slipping between cells but of passing through them, and the endothelial cells are equipped for the task. Oxygen and carbon dioxide, being soluble in fat, diffuse straight through the membrane, which is why anaesthetics and alcohol also reach the brain so quickly. Water passes through dedicated channels. Glucose, which cannot cross on its own, is carried in by a dedicated transporter, and amino acids have their own. In the opposite direction, efflux pumps such as P-glycoprotein seize unwanted molecules and throw them back into the blood, and these pumps are a major reason why so many drugs fail to treat brain disease.
The barrier is not uniform. A handful of small regions, known as the circumventricular organs, have no barrier at all, and this is deliberate. The area postrema, at the base of the fourth ventricle, monitors the blood for toxins and triggers vomiting when it detects them; the median eminence allows hormones from the hypothalamus to enter the bloodstream. The brain needs to sample the blood, in other words, as well as to be protected from it.
In disease the barrier can fail. After a stroke, during an epileptic seizure or in the inflamed patches of multiple sclerosis, the tight junctions loosen and fluid leaks into the tissue, causing swelling that can itself be damaging. Whether the barrier is impaired in Alzheimer's disease is disputed: some studies find leakage, others do not. What is not in doubt is that the barrier blocks treatment as effectively as it blocks infection. The great majority of large-molecule drugs, including antibodies designed to attack brain tumours, cannot enter the brain in useful quantities.
Research has therefore concentrated on ways of getting past it. One approach is to disguise a drug as a molecule the barrier already admits, attaching it to a protein that has its own transporter. Another is to open the barrier briefly. In 2015 a team in Toronto reported the first use in a patient of focused ultrasound, in which pulses of sound combined with microscopic bubbles temporarily loosen the tight junctions at a chosen spot; the procedure has since been tried in small trials for tumours and, experimentally, in Alzheimer's disease. A third line of work is to grow miniature models of brain capillaries on chips, so that drugs can be screened for their ability to cross.
Meanwhile the picture of the barrier has itself changed. In 2012 a group led by the Danish neuroscientist Maiken Nedergaard described a network of channels around the brain's blood vessels through which cerebrospinal fluid flows, carrying away waste products; the flow is greatly increased during sleep. The discovery complicated the older image of a sealed wall. The barrier, it appears, is one part of a system for keeping the brain clean, and how that system behaves in health, in ageing and in disease is still largely unknown.
You should spend about 20 minutes on Questions 27–40, which are based on Reading Passage 3 below.
Should Students Be Allowed to Use Brain-Enhancing Drugs?
A philosopher of education weighs the case for permission and finds it weaker than it first appears
Every autumn, as examinations approach, a proportion of university students take medicines that were not prescribed for them. The drugs in question are stimulants developed to treat attention deficit hyperactivity disorder, and students use them to stay awake, to concentrate for longer and to absorb more in a single night. How many do so is genuinely unclear. Surveys of American campuses have produced estimates ranging from a few per cent to more than a fifth of students, and the figures depend heavily on how the question is asked and on whether students trust the person asking. What is not in doubt is that the practice exists, that passing these drugs to someone without a prescription is illegal in most countries, and that universities have mostly preferred not to look too closely. Should they be permitted?
The case for a permissive approach rests on several claims. The first is autonomy: students are adults, and many of them already use caffeine, alcohol and other substances to alter how they think and feel. The second is consistency. A student who takes a stimulant before an examination is not obviously behaving differently from one who drinks six cups of coffee, and no university proposes to ban coffee. The third is harm reduction. Prohibition does not stop the practice; it merely ensures that students who use these drugs do so secretly, without reliable information about dosage or about the risks of mixing them with other substances, and without anyone to advise them. A fourth is simple realism: the drugs are already in circulation, and no policy will remove them. Whether the drugs sharpen thinking in people who do not have the disorder is disputed; some studies suggest that they mainly increase wakefulness and confidence rather than the ability to reason.
Against this, the medical objections are substantial. Stimulants raise blood pressure and heart rate, disturb sleep and appetite, and can produce anxiety and, in susceptible individuals, psychosis. These risks are accepted in patients who take the drugs under supervision for a diagnosed condition, and who are monitored and can stop if problems appear. A healthy nineteen-year-old who buys a friend's tablets before an examination has none of those safeguards. The long-term effects of regular use on a young brain that does not need the drug are simply not known.
There is also the question of pressure. If a practice becomes normal, students who would rather not use stimulants may feel obliged to do so in order to keep up with classmates who do. This is the strongest argument against permitting them, and it is worth noticing what it implies. The objection is not that the drugs are unfair in themselves but that their widespread use would make an already competitive system worse. The remedy, presumably, is to reduce the pressure rather than to punish those who respond to it.
Many people describe the practice as cheating, and the comparison with doping in sport is often made. I find the comparison unhelpful. Sport is a contest conducted under rules, and a drug that gives one competitor an advantage over another undermines the point of the contest. Education is not a contest of that kind. Degrees are not awarded on a fixed number of places, and a student who revises more effectively does not thereby prevent a classmate from learning. Nor are examinations designed to measure effort; they measure what a student can do on the day. The word 'cheating' does, however, capture something real, namely the discomfort of a system in which some students have a medical shortcut and others do not. That discomfort deserves to be taken seriously, but it is not an argument for prohibition.
In any case, a ban that cannot be enforced is not really a ban. Detecting the use of prescription stimulants requires a blood or urine test, which is intrusive, expensive and, in most institutions, unthinkable for a population of students who have committed no other offence. Nor would testing be reliable: the drugs remain detectable for a limited period, and students would soon learn to take them at times when detection is unlikely. Prohibition would therefore drive the practice underground while achieving very little else, and a rule that is widely broken breeds contempt for rules in general.
A better approach is to regulate rather than to prohibit. Universities should say plainly that they do not recommend the use of these drugs by people who have no medical reason to take them, and should explain why. They should also provide accurate information about what is and is not known, since a vacuum of reliable advice is quickly filled by rumour. Students with a diagnosis should be properly supported rather than treated with suspicion. And institutions should examine their own practices, including the timing of assessments and the culture of relentless competition, which make the drugs attractive in the first place.
My conclusion is therefore an uneasy one. Students should not be expelled or prosecuted for taking these medicines, and universities should not pretend that a prohibition they cannot enforce is a solution. But neither should they shrug and allow it. The honest position is to discourage the practice, to protect those who are most vulnerable to the pressure to conform, and to attack the conditions that make so many students feel that their minds are not quite sufficient on their own.
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