IELTS Academic Reading Practice Test 355

Every year, surgeons around the world replace the clouded lenses of millions of eyes with small discs of plastic. The operation, cataract surgery with the implantation of an intraocular lens, takes only a few minutes under local anaesthetic, and most patients go home the same day. It is easy to forget how recent this is. The first artificial lens was placed inside a human eye in London in 1949, and for years afterwards the surgeon responsible was regarded by many colleagues not as a pioneer but as a reckless experimenter.

Harold Ridley was born in Leicestershire in 1906 and studied medicine at Cambridge before completing his clinical training in London. By the time the Second World War began he had already decided to specialise in ophthalmology, the branch of medicine concerned with the eye. He was then working at Moorfields Eye Hospital, the country's leading centre for the treatment of eye disease. In the early part of the war he treated wounded servicemen there, and it was among these patients that he made the observation on which his later work rested.

Many of the airmen had been hurt when their aircraft crashed, and in some cases tiny pieces of the transparent cockpit canopy had entered their eyes. The canopies were made of a clear acrylic plastic sold under the name Perspex, and the fragments were sharp and difficult to remove. What interested Ridley was that the eye appeared to accept them. In several patients the material remained inside the eye for years, and yet no inflammation developed around it. The tissue simply tolerated a foreign substance that would have caused acute swelling almost anywhere else in the body.

If the eye could tolerate Perspex, Ridley reasoned, a lens made of the same plastic might be left in place permanently. At that time the standard operation for a cataract, the clouding of the lens that slowly destroys sight, was simply to remove the damaged lens. The patient was then given thick glasses, which restored a good deal of vision but magnified everything seen, distorted the edges of the visual field and were heavy to wear. An artificial lens placed inside the eye, Ridley believed, would produce a far more natural result.

On 29 November 1949, in a London hospital, Ridley removed a clouded lens and inserted in its place a small disc of Perspex. The implant had been made by a British optical firm, and he had spent months considering its size, weight and shape. The operation appeared to succeed at first, and the gain in the patient's sight was encouraging. Within a few years, however, some of his early choices looked mistaken: the discs were heavier than the delicate tissues of the eye could comfortably tolerate, and a number worked loose.

The response of the profession was harsh. Ridley's colleagues regarded the idea as dangerous, and at meetings of ophthalmologists his results were criticised in terms that he found deeply wounding. Many surgeons were convinced that inserting a piece of plastic into the eye would cause lasting damage, and that any gain in vision would be outweighed by the risk of blindness. Some of the criticism was reasonable: the complications of those early operations were real, and the techniques of the time could not control them.

Progress came from a small number of surgeons who were prepared to persist. The British surgeon Peter Choyce, among others, spent decades designing lenses that were lighter and more securely fixed, and the operation became safer as operating microscopes, fine sutures and better anaesthesia came into use. A further advance arrived in 1967, when the American ophthalmologist Charles Kelman introduced a technique called phacoemulsification. In this method the clouded lens is broken up with ultrasound and drawn out through an opening only a few millimetres wide. From the 1980s, lenses made of soft materials such as silicone could be folded and inserted through a smaller incision still.

Ridley lived long enough to see the operation he had invented become ordinary. He continued to write about the lens for the rest of his career, and recognition came very late: he was knighted only in 2000, at the age of ninety-three, a year before his death. By then the implantation of an intraocular lens had become a routine part of cataract surgery in every developed country, and the number of such operations performed each year ran into millions.

The story raises a question that recurs throughout the history of medicine: why an idea that now seems obvious was resisted for so long. Part of the answer lies in the belief of the day that the eye would never tolerate a foreign body in its interior, so that any implanted object would sooner or later be rejected. Part lies in memories of earlier failures, when surgeons had tried glass lenses. And part lay in the caution of a profession that had watched many promising innovations end in disaster.

Ridley's contribution was not a new instrument or a new drug but an observation about a material. Perspex had been chosen to protect pilots from flying fragments; that living tissue would tolerate it was a piece of good fortune that made possible an operation performed many millions of times a year. The man who noticed it spent most of his working life being told that he was wrong.

DNA is often described as the instruction manual for a living organism, which makes it sound far more permanent than it is. In reality the molecule is chemically fragile. It reacts with water, with oxygen and with a range of other substances, and it is also exposed to ultraviolet light, to background radiation and to chemicals in the air and in food. Every cell therefore contains a set of enzymes whose only job is to find damaged DNA and put it right. Without them the manual would soon become unreadable.

Researchers often estimate that the DNA in a single human cell suffers thousands of damaging events every day. Some of this damage happens spontaneously: the bond that attaches a base to the backbone of the helix occasionally breaks, and the base is lost. Cytosine, one of the four bases that spell out the genetic code, slowly turns into uracil in a reaction with water. Other damage is caused by molecules known as reactive oxygen species, and by outside agents such as sunlight. Ultraviolet radiation in particular makes neighbouring bases stick together to form a bulky block that distorts the shape of the helix. Breaks in one or both strands also occur, and a double-strand break is the most dangerous of all, because the two ends can drift apart and be lost.

For small changes of the kind caused by water and oxygen, cells use a mechanism called base excision repair. The first step is carried out by an enzyme, a DNA glycosylase, which recognises a particular kind of damaged base and removes it, leaving a gap in the sequence. Other enzymes then cut the backbone at that point, and a third set, the polymerases, rebuild the missing piece using the undamaged strand as a template. Finally a ligase seals the join. The result is a repair so accurate that the original sequence is restored exactly, and only the faulty base and a few of its neighbours are replaced.

Larger distortions need a different approach. When ultraviolet light creates a bulky lesion, or when a chemical attaches itself to a base, the problem is not a single wrong letter but a lump that prevents the helix from being read. Nucleotide excision repair deals with this by removing a stretch of the damaged strand, about 25 to 30 bases long, around the lesion, and then filling the gap from the intact strand. The importance of this pathway is illustrated by a rare inherited disorder, xeroderma pigmentosum, in which the repair proteins are defective. People with the condition cannot repair damage caused by sunlight, and they develop skin cancers after very little exposure to the sun.

The cell faces a different problem when DNA is copied before division. Copying is accurate but not perfect, and mistakes inevitably occur. Mismatch repair patrols the newly made strand and looks for pairs of bases that do not belong together. Because it must decide which of the two strands is the correct one, it relies on chemical marks that distinguish the new copy from the old template, and in human cells the details of that labelling are still not fully understood. The consequences of failure are serious: inherited faults in mismatch repair cause a form of bowel cancer that often develops at an unusually early age.

The most serious damage is a break across both strands of the helix. Two mechanisms exist, and they are very different in character. Homologous recombination uses an undamaged copy of the DNA — the matching chromosome, or a sister chromatid produced during the copying phase — as a template, and it restores the original sequence with great precision; it is, however, available only at certain stages of the cell's life. Non-homologous end joining is faster and can be used at any time: it grabs the two broken ends and sticks them back together. The price of speed is accuracy, and a few bases are often lost or altered at the join. Inherited faults in homologous recombination are associated with some breast and ovarian cancers.

Repair is only one part of the response. When damage is detected, proteins at the cell's checkpoints can halt the cycle of division until the repairs are finished, giving the enzymes time to work. If the damage is too extensive, the cell may be instructed to destroy itself, a form of programmed suicide that protects the rest of the tissue from a cell carrying a dangerous mutation. The protein p53 sits at the centre of this decision and is known, for good reason, as the guardian of the genome.

Much remains uncertain. Chief among the puzzles is how repair proteins locate damage so quickly in a genome of three billion base pairs; several explanations have been proposed, and none commands general agreement. Researchers would also like to know why the capacity to repair DNA appears to decline with age, and how much of the variation between individuals is inherited. The medical interest is considerable. Drugs called PARP inhibitors, used against some ovarian and breast tumours, work by blocking a repair pathway on which the cancer cells have come to depend after losing another. The 2015 Nobel Prize in Chemistry, awarded to Tomas Lindahl, Paul Modrich and Aziz Sancar, recognised how much of this machinery had been mapped.

Within a few days of birth, a midwife in most wealthy countries takes a few drops of blood from a baby's heel and sends them to a laboratory. The sample is tested for a small number of conditions, such as phenylketonuria and congenital hypothyroidism, for which early treatment prevents severe disability. Screening of this kind began in the 1960s and has quietly prevented a great deal of suffering. Now a much more ambitious proposal is being discussed: instead of testing for a handful of conditions, why not read the whole of each baby's genetic code, once, at the beginning of life?

The technology is certainly available. A human genome can now be sequenced in a few days for a small fraction of what it cost twenty years ago, and the price continues to fall. Sequencing a newborn's whole genome would reveal far more than the conditions already screened for. It would also show thousands of variants linked, more or less strongly, to diseases that may appear in childhood or in old age. For a baby who is already ill the benefit can be dramatic. In intensive care units, rapid sequencing has given a diagnosis within days for some infants whose condition had baffled their doctors, and has occasionally changed the treatment they received. The question is whether that success justifies sequencing every healthy baby.

The strongest argument against universal sequencing is that most of the information it produces cannot yet be interpreted. A genome contains millions of differences from the reference sequence, the great majority of them harmless. For a large proportion of the variants that look suspicious, no one can say whether they matter. A family may be told that their child carries a variant of uncertain significance and then spend years wondering what it means. Even where a risk is real it is usually a statistical one: a raised chance of a condition that may never develop. Medicine is not yet good at communicating probabilities of this kind, and parents are rarely in a position to weigh them.

There are also practical harms. A child labelled as being at risk may be subjected to repeated tests and appointments for a condition that never appears, a situation that researchers sometimes call the patient in waiting. Parents may become anxious, and brothers and sisters may be tested for the same variant. Privacy is a further concern. Genetic information is shared with relatives and cannot be revised or withdrawn. In the United States, a federal law passed in 2008 prevents health insurers and employers from using genetic data, but it does not cover life insurance, disability insurance or long-term care insurance, and a family that discovers a serious risk may find that its choices in those markets are affected.

Then there is the question of consent. A newborn cannot agree to anything. Parents are asked to decide on their child's behalf, which is reasonable where an immediate treatment is at stake but less obviously so for information that may matter in forty years. Testing a baby for a condition that can be treated at once is quite different from handing a family a file of risks that will not become relevant until adulthood. The child's right to an open future, to decide in adulthood what to find out about themselves, is a serious argument for restraint.

Against these concerns stands a broader claim about fairness. If sequencing is offered at all, it will be offered first to those who can pay for it, and a service available only in private clinics would widen the gap between families who can act on genetic information and those who cannot. There is also a research interest. A national programme linking genomic data to medical records could produce knowledge that benefits everybody. Some governments have concluded that the public good justifies a large public effort. England, for example, has announced a programme intended to sequence the genomes of 100,000 babies, with the explicit aim of studying both the benefits and the difficulties.

The design of such a programme matters more than its size. Consent should be explicit, and parents should be able to choose between a narrow test that looks only for conditions that can be treated in childhood and a broader one that may reveal risks decades later. Results should be returned by people trained to explain uncertainty, and children should be free to withdraw their data when they reach adulthood. Storage must be secure, and access by insurers, employers and the police should be defined by law rather than left to chance. None of this is impossible; it is simply expensive and unglamorous.

My own view is that the case for sequencing every newborn has not been made. The evidence of benefit for healthy babies is thin, the harms are real though hard to measure, and the science of interpretation is changing fast enough that information gathered today may look very different in ten years. Where sequencing has proved its worth is in sick infants, whose diagnosis cannot wait, and in a few treatable conditions of childhood. Beyond that, the sensible course is to run carefully governed studies with long follow-up rather than to promise parents a complete picture of their child's future. A genome is not a prognosis.