IELTS Academic Reading Practice Test 353

Until the middle of the twentieth century, couples who wished to limit the size of their families had few reliable options. Condoms depended on the cooperation of the man, and withdrawal demanded considerable self-control. The rhythm method, which meant avoiding intercourse on the days when a woman was thought to be fertile, rested on a poor understanding of the menstrual cycle. In the United States the distribution of information about contraception had been restricted by federal law since 1873. It was against this background that a small group of scientists and campaigners set out to create something that had never existed: a pill that would allow a woman to control her own fertility.

The campaigner was Margaret Sanger, who had spent decades promoting birth control and had been prosecuted for it. In the early 1950s she turned to an old ally, Katharine McCormick, a wealthy widow who had studied biology at the Massachusetts Institute of Technology and shared her ambitions. McCormick was willing to pay for research, and it was Sanger who introduced her to Gregory Pincus, a biologist who had already made his name with experiments on the fertilisation of rabbit eggs. Pincus worked at the Worcester Foundation for Experimental Biology in Shrewsbury, Massachusetts, and McCormick's money allowed him to begin the work that would occupy the rest of his career.

Pincus's partner in the clinical work was John Rock, a Boston gynaecologist who was also a devout Catholic. Rock had been using synthetic hormones to treat women who could not conceive, and he was prepared to accept that the same substances might prevent pregnancy. Two chemical advances made the project possible. Progesterone prepares the lining of the womb for pregnancy and suppresses ovulation while a pregnancy is being established. It had been shown in the 1930s to stop ovulation when given in large doses. But it was expensive, had to be injected and was rapidly broken down by the body.

The second advance was the synthesis of progestins that could be swallowed. In 1951 Carl Djerassi and his colleagues at a small company called Syntex, working in Mexico City, produced a compound they named norethindrone. They made it from a substance extracted from a wild Mexican yam. Chemists at the American firm G. D. Searle, among them Frank Colton, independently made a very similar compound, norethynodrel. These synthetic progestins survived digestion, were far cheaper to manufacture than the natural hormone and could be taken in tablet form.

Clinical testing began cautiously. Pincus and Rock first gave the drug to women in Boston who were being treated for infertility, and then, wanting a larger and more closely observed group, moved their main trial to Puerto Rico. There a physician named Edris Rice-Wray supervised a study in a housing project in Rio Piedras. Pregnancy was almost entirely prevented, but many of the women reported nausea, headaches and other complaints, and some stopped taking the tablets. The doses then in use were several times higher than those thought necessary today.

The drug had been on the market since 1957 under the name Enovid, officially for menstrual disorders, and many American doctors had already been prescribing it to married women who wanted no more children. In 1960 the Food and Drug Administration approved it for contraception, and within a few years it was being taken by millions of women across the country. That a Catholic gynaecologist had helped to develop the pill gave it a respectability it might otherwise have lacked, although Rock's own church eventually condemned the method.

Elsewhere the change came almost as quickly. In Britain the pill was available through the National Health Service from 1961, at first largely to married women, and in practice some family doctors refused to prescribe it. The Family Planning Act of 1967 allowed local authorities to provide contraceptive advice and supplies, and from 1974 the pill was free to all women on the NHS.

The pill's safety record was tested in public. It soon became clear that the high doses of oestrogen in the early formulations were associated with an increased risk of blood clots, particularly in women who smoked. In 1969 the writer Barbara Seaman published a book arguing that women had been used as experimental subjects. In 1970 a Senate subcommittee chaired by Gaylord Nelson held hearings on the pill's safety, which were disrupted by protesters complaining that no women who took the pill had been invited to testify. Manufacturers responded by reducing the dose of oestrogen. A similar alarm occurred in Britain in 1995, when a warning about the risk of clotting with certain newer progestins led many women to stop taking the pill, and unplanned pregnancies rose.

Historians still argue about how much of the social change of the 1960s and 1970s can be attributed to a single tablet. They point to rising ages at marriage, growing numbers of women in higher education and smaller families, while noting that such trends had begun before 1960. What is not in doubt is its reach. The combined oral contraceptive appears on the World Health Organization's list of essential medicines and is used by well over a hundred million women. Access, however, remains uneven: in some countries supplies are scarce, and in others the method is regarded with suspicion.

Few organs are as temporary as the placenta, which forms inside the uterus during pregnancy and is delivered a few minutes after the baby, which is why it is often called the afterbirth. It begins to grow within days of fertilisation, when the embryo is smaller than a grain of sand, and by the end of pregnancy it weighs roughly a sixth as much as the child it has supported. Lying against the wall of the uterus and joined to the fetus by the umbilical cord, it performs the work of several organs at once: lungs, gut, kidneys and a large part of the endocrine system.

Implantation begins about six or seven days after fertilisation. The outer cells of the blastocyst, the hollow ball of cells that will become the baby, are called the trophoblast, and it is these cells that give rise to the placenta. Some of them fuse to form the syncytiotrophoblast, a single continuous layer that contains many nuclei and has no internal cell boundaries. This layer is invasive in a way that few human tissues are. It digests its way into the lining of the uterus and then into the walls of the mother's spiral arteries, remodelling them into wide, floppy vessels. Maternal blood then flows into open spaces around the placental tissue, bathing the fetal side of the organ.

The exchange itself takes place in villi, thousands of finger-like projections that grow out from the fetal side into those blood-filled spaces. The villi branch repeatedly, and their combined surface area is large, which matters because the rate of exchange depends on how much surface is available. Between the two circulations lies the placental barrier, a thin sheet of tissue that separates maternal blood from fetal blood. The two never mix. This is one of the most important facts about the organ, and it explains how a mother and her fetus can have different blood groups without immediate catastrophe.

Oxygen is carried across the barrier by simple diffusion, moving from the maternal blood, where its concentration is higher, to the fetal blood, where it is lower. Carbon dioxide, produced by the fetus, travels in the opposite direction. Glucose, the fetus's main fuel, is transferred by facilitated diffusion, which requires transporter proteins in the barrier and cannot exceed the maternal concentration. Amino acids, by contrast, are actively pumped across, and fetal levels of some of them are higher than maternal ones. Fatty acids, vitamins and minerals follow their own routes, some of them assisted by proteins that bind to them.

The placenta is also an endocrine gland of remarkable output. In the first weeks it secretes human chorionic gonadotrophin, or hCG. This hormone travels to the mother's ovary and keeps the corpus luteum, the structure left behind after ovulation, from breaking down, so that it goes on releasing progesterone. hCG appears in the mother's urine, which is why home pregnancy tests can detect it. From about the tenth week the placenta itself produces most of the progesterone needed to maintain the pregnancy. Later it releases human placental lactogen, a hormone that makes the mother's tissues less responsive to insulin, raising the level of glucose in her blood so that more is available for the fetus. This is thought to be one reason why some women develop diabetes during pregnancy.

Antibodies of the class known as IgG are taken up by cells of the syncytiotrophoblast and delivered to the fetus, giving the newborn some protection against infection during its first months. Most bacteria are too large, or lack the means, to cross. Several viruses, however, can pass, among them rubella, cytomegalovirus and Zika, and some of these can damage the developing fetus. Alcohol and many drugs cross in a similar way, which is why pregnant women are advised to avoid them. Vaccinating a woman during pregnancy therefore protects two people: her and, for a while, her baby.

When the organ develops abnormally, both mother and baby suffer. Pre-eclampsia, a condition marked by high blood pressure and damage to organs such as the kidneys and liver, is associated with a placenta that lies too shallowly in the uterine wall. The mother's arteries are then only partly remodelled. Fetal growth restriction can follow. At the other extreme lies placenta accreta, in which the placenta grows too deeply into the uterus and fails to separate after birth, sometimes causing dangerous bleeding.

Research on the placenta is difficult for obvious reasons. It is one thing to study a tissue in a laboratory dish and another to follow it while it is working inside a pregnant woman, and the ethical limits on such research are, rightly, strict. Much of what remains unknown concerns the last weeks of pregnancy: what triggers labour, and why the organ begins to age and fail in some pregnancies but not others. A growing body of evidence also links the placenta to the health of the child decades later. To investigate such questions, scientists have built 'placenta-on-a-chip' devices. In these, a layer of placental cells and a layer of vessel cells grow in a narrow channel, separated by a membrane, so that substances can be tested as they cross.

When a new drug for hepatitis C reached the American market in 2013 at a list price of $84,000 for a twelve-week course, the reaction was unusually fierce. The treatment cured more than nine out of ten patients, yet analyses suggested that making it cost a small fraction of that sum. Similar arguments have surrounded insulin, cancer therapies and, more recently, treatments for rare diseases. The disagreement is not about whether new medicines are expensive, since everybody agrees that they are. It is about who should decide how much a health system pays, and on what basis.

A new medicine must pass through years of laboratory work and three phases of human trials, and the great majority of the compounds that enter development are abandoned. A widely quoted analysis published in 2016 put the average cost of a successful medicine at about $2.6 billion. That figure includes the cost of the failures and the profits investors forgo during the years of testing. Critics point out that such estimates depend heavily on assumptions, but few deny that the work is expensive and uncertain. Companies argue that the patent system, which grants a temporary monopoly, exists precisely to make that risk worth taking, and that if prices are capped, investment will flow towards industries with better returns.

Against this, it should be remembered that a patent is not a natural right but a privilege granted by the state. Governments pay for much of the basic science on which modern medicines depend, and for most of the treatment. A national health service is also in an unusual position, buying on behalf of millions of people at once. When one purchaser accounts for such a large share of a company's sales, it is hardly surprising that it wants to influence the price. Nor is there much doubt that it can. The same medicines often cost several times more in the United States, where public programmes have until recently had little power to negotiate, than in Europe.

Setting prices well, however, is not simply a matter of choosing a number. Since 1999 the National Institute for Health and Care Excellence has assessed new drugs and recommended them for the health service only when their benefits justify their cost. It uses a measure known as the quality-adjusted life year, which combines extra length of life with its quality. Germany has since 2011 required manufacturers to demonstrate that a new medicine offers an advantage over existing ones before a price is agreed. In both countries, the question is not what a medicine costs but what it is worth.

Negotiations of this kind favour medicines whose benefits are easy to measure. A drug that keeps a patient alive for a few more months can look better value than one that prevents a rare complication. Confidential discounts, increasingly common in Europe, keep the official price high and the real price secret. They suit manufacturers and health systems alike, but they make it impossible for outsiders to judge whether the taxpayer is getting a fair deal.

Price is also a global question. Under the trade rules agreed in the 1990s, countries must offer patent protection. A declaration issued by the World Trade Organization at Doha in 2001, however, confirmed that the rules should not prevent governments from protecting public health, including by overriding a patent. India used this route in 2012 to license a cheap copy of a cancer drug. Yet compulsory licences are a blunt instrument, and companies have sometimes responded by refusing to launch products in markets they consider unprofitable. Poorer countries therefore rely more on voluntary schemes in which firms charge different prices in different regions.

The hardest case is antibiotics. A new antibiotic must be held in reserve to slow the development of resistance, so a successful one sells very little by design. Sales-based rewards therefore fail exactly where they are most needed, and many large companies have abandoned the field. In England the health service has tested a different approach, paying a fixed annual sum for access to a new antibiotic regardless of how much is used. The reward then depends on value rather than volume.

How much difference any of this makes to innovation is genuinely uncertain. Pharmaceutical research is global and slow, and it is difficult to know what would have been discovered if prices had been lower or higher, since there is no way to run the experiment twice. Economists disagree about whether recent investment in new fields reflects the pull of high prices or the push of better science, and the decisions companies make are rarely visible to outsiders.

My own view is that governments should indeed set or negotiate the prices of medicines, because the alternative is to let a monopoly charge what it wishes with public money. But the process should be built on evidence of benefit, conducted transparently, and designed to reward treatments that genuinely improve on what exists rather than those that are merely newer. Price policy will not, on its own, deliver medicines to everyone who needs them. It is, however, the part of the problem that governments can most easily control.