IELTS Academic Reading Practice Test 324

Vitamin B12 is a substance that the human body needs in almost unimaginably small quantities yet cannot manufacture for itself. Without it, the bone marrow produces too few red blood cells and the nerves slowly deteriorate. The resulting condition, pernicious anaemia, was for centuries invariably fatal. In 1926 two American physicians, George Minot and William Murphy, showed that patients could be kept alive by eating large quantities of raw liver, work for which they later shared the Nobel Prize in Physiology or Medicine. Nobody knew what the liver contained.

The answer emerged only in 1948, when research teams at two pharmaceutical companies, one American and one British, independently isolated minute quantities of red crystals from liver. It was named vitamin B12, and it proved astonishingly potent: a few millionths of a gram a day could restore a patient's blood to normal. The amounts available were tiny, however, and the molecule was plainly complicated. Working out the arrangement of its atoms would demand an unusual technique and an unusually patient chemist.

Dorothy Crowfoot Hodgkin was born in Cairo in 1910, where her father worked in the Egyptian education service, and was sent to school in England. She read chemistry at Somerville College, Oxford, and then moved to Cambridge, where she completed a doctorate under the crystallographer J. D. Bernal. There she learned to fire beams of X-rays at crystals and to work backwards from the patterns they produced to the positions of the atoms inside. Bernal's laboratory was one of the few places applying the technique to biological molecules.

In 1934 Hodgkin and Bernal obtained the first X-ray diffraction photograph of a protein, a crystal of the digestive enzyme pepsin. Until then, most scientists had assumed that protein molecules were too irregular to form crystals of any use. The photograph was sharp and detailed, which showed that proteins, for all their size, are built on a regular plan. The result opened the way to protein crystallography, a field that would later transform biology.

The method works because the distance between atoms is comparable to the wavelength of X-rays. When a beam strikes a crystal, the atoms scatter it, and the scattered waves reinforce one another in particular directions, leaving a pattern of spots on a photographic film. The positions of the spots reveal the geometry of the repeating unit; their brightness carries further information. The difficulty is that the film records only the strength of each wave, not its phase, and without phases the picture cannot be reconstructed.

Hodgkin, by then back at Oxford, was among the first to take up the challenge of vitamin B12. Elementary analysis of the crystals indicated the presence of cobalt, a metal almost never found in living things, together with a cyanide group picked up during the isolation process. The molecule was also enormous by the standards of the day. Its mass is roughly seventy-five times that of a water molecule, and it contains more than ninety atoms besides hydrogen. Pharmaceutical companies supplied the precious crystals, and Hodgkin's group began work in 1948.

The work was laborious. Each crystal produced a pattern of spots that had to be measured, and thousands were needed before an image could be attempted. The intensities were estimated by eye from the films, and the arithmetic that followed was carried out by teams of assistants using mechanical calculators and punched-card machines. The key to the whole enterprise was the cobalt atom. Being far heavier than carbon, nitrogen or oxygen, it dominates the scattering and could be located first; once its position was known, its contribution could be used to estimate the phases of the other atoms.

By 1955 Hodgkin and her colleagues had gathered enough data to read the structure, and they announced it at a meeting that year before publishing a full account in 1956. At the centre of the molecule sits the cobalt atom, held within a ring of carbon and nitrogen atoms that became known as the corrin ring. Around this ring hang sugar, phosphate and other groups. The corrin ring resembles the porphyrin ring of haemoglobin, the pigment that carries oxygen in blood, but it is not identical: one carbon atom is missing, which gives the molecule its distinctive shape and allows it to carry chemical groups into reactions catalysed by enzymes.

Vitamin B12 was the most complex structure ever determined by X-ray methods at the time, and it made Hodgkin famous far beyond her own subject. She was awarded the Nobel Prize in Chemistry in 1964, becoming the third woman to receive it, after Marie Curie and Irène Joliot-Curie. She had already helped to establish the structure of penicillin in the mid-1940s, and she would spend another twenty years on insulin, a structure finally solved in 1969, thirty-five years after the pepsin photograph.

Hodgkin had suffered from rheumatoid arthritis since her late twenties, and by the 1960s her hands were badly deformed; visitors to her laboratory remember her directing work that she could no longer perform herself. She died in 1994. In 1972, Robert Burns Woodward and Albert Eschenmoser completed a synthesis of vitamin B12 in the laboratory, a landmark of organic chemistry that depended on knowing the structure Hodgkin had revealed.

The knee is the largest joint in the human body, and it is usually described as a hinge. In reality it is more complex than a door hinge, because it must allow the leg to swing, bear weight and rotate slightly when the body turns. Three bones meet there: the femur, or thigh bone, above; the tibia, or shin bone, below; and the patella, or kneecap, at the front. The smaller fibula runs alongside the tibia but takes no part in the joint itself.

The ends of the femur and tibia are covered by articular cartilage, a smooth, whitish tissue a few millimetres thick that cushions the bones and lets them slide over each other. Cartilage contains no blood vessels and no nerves. Its living cells, called chondrocytes, are scattered sparsely through a dense matrix of collagen and water-holding molecules. Having no blood supply of its own, it must be fed by the fluid around it, and it heals poorly when damaged. Its coefficient of friction is lower than that of ice sliding on ice.

Between the two bones lie the menisci, two crescent-shaped pads of fibrocartilage that rest on the flat top of the tibia. They deepen the surface on which the femur rests and spread the load over a wider area, rather like a washer under a nut. They also help to distribute the synovial fluid across the surfaces of the joint. Their outer edges have a blood supply, but the inner two-thirds do not, which is one reason why a tear near the centre of a meniscus is slow to heal and may never do so.

The bones are held together by ligaments. Inside the joint, two strong bands called the cruciate ligaments cross each other, preventing the tibia from sliding forwards or backwards under the femur. On either side of the knee run the collateral ligaments, which resist forces that would bend the joint sideways. A fibrous capsule encloses the whole structure.

The inner surface of the capsule is lined by the synovial membrane, which secretes synovial fluid. This pale, yellowish liquid does three jobs: it lubricates the moving surfaces, supplies the cartilage with nutrients and carries away waste. Its behaviour is unusual. A simple liquid such as water resists flow equally at any speed, whereas synovial fluid becomes thinner the faster the joint moves. The effect is that the fluid offers little resistance during a quick stride, yet remains thick enough to cushion the joint when a person stands still.

Movement comes from muscles that attach to the bones by tendons. The quadriceps, at the front of the thigh, straightens the leg; the hamstrings, at the back, bend it. The patella is the largest of the body's sesamoid bones — bones that develop inside a tendon — and it is embedded in the tendon of the quadriceps. By holding that tendon away from the centre of the joint, it increases the leverage of the muscle, so that less force is needed to straighten the leg.

The loads involved are considerable. Walking places a force of about two and a half to three times body weight on the joint with each step. Climbing stairs raises that figure to roughly four times body weight, and rising from a low chair raises it further. Cartilage survives this because most of it is water held inside a mesh of collagen and proteoglycan molecules. When the joint is loaded, some of the water is squeezed out; when the load is removed, it flows back. This pumping action also helps to nourish the tissue, which is why regular movement is good for cartilage and prolonged immobility is not. Much of what is known about these forces comes from instruments built into artificial joints.

Injuries are common. The anterior cruciate ligament is most often torn in sports that involve sudden stops and pivots, such as football and skiing, and meniscal tears are frequent in middle age, sometimes after no obvious accident. Osteoarthritis, in which cartilage thins and the whole joint gradually changes, is among the most widespread of chronic conditions; it becomes more common with age and with excess body weight, which increases the load the joint must bear.

Much remains uncertain. Imaging studies have repeatedly found that many people whose scans show a torn meniscus or worn cartilage feel no pain at all, while others with little visible damage are in constant discomfort. The link between what a scan shows and what a patient experiences is therefore weaker than most people assume. Research on repairing cartilage is active but so far modest in its results: laboratory-grown cartilage cells, implanted scaffolds and injectable gels have all been tried, and none has yet restored a worn joint to its original state.

Current work concentrates on prevention as much as repair: strengthening the muscles around the knee, retraining the way people walk and jump, and using wearable sensors to measure load in everyday life. Surgery can mend a torn ligament or replace a worn joint, but it is a last resort rather than a cure. For most people, the most effective treatment remains the least dramatic — keeping the joint moving, and keeping the weight it carries within reason.

Among the world's richer countries, only two allow pharmaceutical companies to advertise prescription medicines to the public: the United States and New Zealand. Everywhere else — across the European Union, Canada, Australia and Japan — such advertising is prohibited, and companies may promote their products only to doctors. The American market is by far the largest, and it is there that the consequences of what is called direct-to-consumer advertising can best be judged. Companies there spend billions of dollars a year on such campaigns, sums that grew rapidly after the regulator relaxed its rules on broadcast advertising in 1997. New Zealand has reviewed the practice more than once without abolishing it.

The argument in favour rests on information. Supporters point out that many serious conditions, including high blood pressure, depression and asthma, go undiagnosed for years, and that people who might never mention a symptom to a doctor may be prompted to do so by an advertisement. Advertising, they contend, reduces stigma by showing that a condition is common and treatable, and it treats patients as adults capable of taking part in decisions about their own care. Surveys in the United States have found that a substantial minority of patients say an advertisement led them to consult a doctor about something they had not previously discussed.

The difficulty is that an advertisement is not a balanced piece of health education. In the United States, television commercials for prescription medicines must include a statement of the most important risks and must make 'adequate provision' for viewers to find further information, usually by naming a website or a free telephone number. In practice this produces a curious performance: a minute of warm images and confident claims, followed by a rapid recital of side effects, some of them serious. Studies of recall have generally found that viewers remember the benefits far better than the risks. The regulator has required companies to withdraw or correct advertisements that overstated the benefits of a product, but such action comes after the campaign has run.

The commercial purpose of advertising is to sell a particular product, and it shapes prescribing accordingly. The medicines most heavily promoted are almost always the newest, which are usually the most expensive and are often no more effective than older drugs costing a fraction as much. Doctors report that patients arrive asking for a brand they have seen on television, and that persuading them to accept a cheaper equivalent takes time. Analyses of prescribing have found that advertising is associated with faster uptake of the drugs promoted and with higher spending, though the size of the effect is disputed.

Sometimes the consequences have been grave. The promotion of prescription opioid painkillers in the United States in the late 1990s and 2000s, which played down the risk of addiction, is widely regarded as one of the forces behind an epidemic of dependence that has killed many thousands of people; in 2007 the manufacturer of one such drug pleaded guilty to criminal charges of misbranding it. In 2004 the painkiller rofecoxib, heavily advertised before its withdrawal, was taken off the market because of an increased risk of heart attack and stroke. Both cases became arguments for stricter control of promotion rather than for its abolition.

Yet a simple ban is not the complete answer either. Promotion does not stop when advertising stops; it moves to the consulting room, to sponsored medical education and to the pages of journals, where the public cannot see it. Disease-awareness campaigns, which discuss a condition without naming a product, are permitted in Europe and are widely understood to be marketing by another name. Meanwhile patients search the internet, and arrive at surgeries with printouts from websites of unknown provenance, which doctors then have to correct. A rule that keeps commercial voices off the airwaves while leaving the field to unregulated websites may protect the letter of the law and very little else.

My own view is that the choice is not between prohibition and the American system. A regulated middle course would serve patients better than either. Advertising of prescription medicines should require the prior approval of an independent regulator, and information about risks should be given prominence equal to that given to benefits, in plain language, without music, celebrities or images of happy families. Newly approved drugs should not be advertised at all until enough evidence about their safety has accumulated, and no advertisement should name a brand where an equivalent generic medicine exists. Money currently spent on promotion would be better used for independent information, written by people with no product to sell.

None of this will satisfy the industry, which will argue that any restriction limits its freedom to speak to the public. But a commercial interest in selling a particular product is not the same as the public interest in being informed, and the two have been confused for too long. Advertising medicines to patients is not in itself indefensible. It becomes indefensible when the seller controls the message and the regulator arrives afterwards. The test is not whether such advertising exists, but who sets its terms.