IELTS Academic Reading Practice Test 385

Malaria has killed more people than any other infectious disease in history, and in the middle of the twentieth century it seemed to be losing ground. The insecticide DDT had wiped out the mosquitoes that carry the parasite in many countries, and the drug chloroquine cured patients cheaply and quickly. By the 1960s, however, both were failing. Mosquitoes were becoming resistant to DDT, and strains of the malaria parasite were surviving chloroquine. The problem was urgent in South-East Asia, where soldiers on both sides of the Vietnam War were falling ill in large numbers.

In May 1967 the Chinese government launched a secret research programme to find new antimalarial drugs. It was given the name Project 523, after the date on which it was approved — 23 May. Institutes across the country were asked to contribute, and the task of investigating traditional herbal remedies fell to the China Academy of Traditional Chinese Medicine in Beijing. A young researcher there, Tu Youyou, was appointed to lead the work in 1969. Tu had been born in Ningbo in 1930, had trained in pharmaceutical sciences and had spent years studying the chemistry of medicinal plants.

Tu began by reading the classical texts of Chinese medicine and compiling lists of plants said to relieve fever, the most familiar symptom of malaria. Her team tested hundreds of herbal preparations on infected mice, but the results were disappointing. One plant, however, appeared repeatedly in the old literature and sometimes gave a faint positive result. This was qinghao, sweet wormwood, whose use against fevers was described in a handbook compiled by the physician Ge Hong in the fourth century. Sweet wormwood is a common weed of waste ground, and its leaves have a strong smell. Ge Hong recommended soaking the herb in cold water, wringing it out and drinking the juice — an instruction that struck Tu as unusual, because most remedies in these texts were boiled.

That detail proved decisive. Tu suspected that the active substance was being destroyed by heat, and her team's earlier method had indeed involved boiling. In 1971 she changed the process: the leaves were extracted with ether at a low temperature instead. The new extracts were tested in the laboratory, and the results were poor until, at the 191st attempt, the extract eliminated the parasites completely in infected mice and monkeys.

The active substance was isolated as colourless crystals in 1972 and given the name qinghaosu; outside China it became known as artemisinin. The Chinese name identifies the compound as an extract of qinghao. Its molecular structure was determined over the following years and described in the Chinese scientific press in 1977 without individual authors, because the compound was regarded as a collective achievement. The structure turned out to be unusual: a small folded molecule containing a peroxide group, two oxygen atoms joined to each other, a feature rare among natural products and one that later proved essential to the drug's action.

Before the drug could be given to patients, its safety had to be checked. Tu and several colleagues took the first doses themselves and reported no serious harm. The team then travelled to Hainan, an island province where malaria was widespread, and treated patients with artemisinin during the early 1970s. Patients with fever and high parasite counts recovered quickly, and the drug worked against strains that had become resistant to chloroquine.

Recognition came slowly. For years the discovery was known only within China, and the results appeared in Chinese journals that few foreign scientists read. Derivatives that were easier to give, such as artesunate and artemether, were developed in China in the late 1970s and 1980s, and interest abroad grew as chloroquine resistance spread across Africa. The World Health Organization recommended combination therapies based on artemisinin in 2001, and the treatment became standard across the tropics. Tu received the Lasker award in 2011 and the Nobel Prize in Physiology or Medicine in 2015, at the age of 84, sharing the latter with William Campbell and Satoshi Ōmura.

Artemisinin is a fast-acting drug but a fragile one: used alone it is cleared from the body quickly, and parasites can survive if it is given carelessly. It is therefore combined with a slower partner drug that finishes the job, and these artemisinin-based combination therapies are now used almost everywhere that malaria is treated. The partner drugs, such as lumefantrine and amodiaquine, clear the remaining parasites more slowly but more thoroughly. The World Health Organization estimates that more than ten million lives have been saved since 2000, most of them in sub-Saharan Africa, and much of that improvement is credited to these combinations and to insecticide-treated bed nets.

The work is not finished. During the 2000s, parasites in the Greater Mekong subregion began to take longer to clear from patients treated with the combination therapies, a sign of partial resistance, and since about 2020 similar evidence has emerged in parts of East Africa. Scientists are searching for new drugs, and several candidates are in development. Tu has continued to work in Beijing and has argued that the old texts remain a source of ideas. No patent was taken out on artemisinin in China at the time, a decision that helped to keep the drug cheap and widely available.

Plants cannot run away. Because they must endure whatever eats them, competes with them or infects them, they have evolved an extraordinary chemical repertoire, and estimates of the number of distinct compounds they manufacture exceed 200,000. Most of these substances play no part in growth or in the capture of energy. They are known as secondary metabolites, and they serve the plant as poisons, deterrents, signals and sunscreens. The same chemicals have proved invaluable to medicine. Aspirin descends from a compound in willow bark, morphine comes from the opium poppy, quinine from the bark of cinchona trees and digoxin from foxgloves. Some, such as the cardiac glycosides of foxgloves, are powerful enough to be dangerous, and the gap between a dose that helps and one that harms is narrow.

Chemists group these compounds into a few large families, three of which account for most drugs. Alkaloids contain nitrogen and are often bitter or toxic; the family includes caffeine, nicotine, morphine, quinine and the anticancer drugs vincristine and vinblastine. Terpenoids are assembled from five-carbon units and range from the volatile oils that give mint and pine their scent to rubber, steroids and artemisinin, the antimalarial obtained from sweet wormwood, which is a sesquiterpene lactone and therefore a terpenoid. Phenolics, the third family, contain a ring of carbon atoms bearing an oxygen and a hydrogen; they include tannins, the flavonoids responsible for many flower colours, and lignin, which stiffens cell walls. Lignin, a phenolic polymer, makes up a large share of the dry weight of wood.

Making these molecules requires the plant to divert materials and energy from primary metabolism. Alkaloids are built from amino acids such as tryptophan, tyrosine and lysine, which are stripped of parts of their structure and rearranged by a succession of enzymes. Terpenoids are made from isopentenyl pyrophosphate, a five-carbon building block produced by two separate routes: the mevalonate pathway in the cytosol and the methylerythritol phosphate pathway inside plastids. Most phenolics, by contrast, are built by the shikimate pathway, which also supplies the aromatic amino acids. Each step is controlled by a gene, and identifying those genes has been slow work. Because the enzymes act in sequence, a single missing step can leave a plant unable to complete the molecule.

Manufacturing chemical weapons is expensive, and plants do not do it unless they must. Many compounds are produced only after damage or attack: a caterpillar biting a leaf triggers a burst of the plant hormone jasmonate, which switches on the relevant genes within hours. Others are made continuously but stored where they can do no harm, in vacuoles inside cells or in glandular hairs, called trichomes, on the surface of leaves. Mint and tomato plants cover their leaves with trichomes, and so does sweet wormwood. When the tissue is crushed, the stored compound meets the enzyme that converts it into its active form.

Even when a plant makes a promising substance, it usually makes very little of it. The bark of the Pacific yew, source of the anticancer drug paclitaxel, contains the compound in such minute quantities that supplies were desperately short when clinical trials began in the 1980s, and other sources had to be found. The concentration of artemisinin in the leaves of sweet wormwood is also low, generally well under one per cent of dry weight, and it varies greatly between plants. Extraction is also laborious, since the harvested leaves must be dried, treated with solvents and purified, all of which adds to the cost. This is one reason why medicines based on plants have so often been expensive to produce.

The variation is not simply random. The quantity of a medicinal compound depends on the plant's genes and on the conditions in which it grows: light, water, temperature, soil and altitude can all change it. Farmers who grow sweet wormwood for the pharmaceutical industry, in China, Vietnam and East Africa, must therefore select high-yielding varieties and harvest at the moment when the concentration peaks, which is usually just before the plant flowers. In ginseng, the concentration of the active compounds is known to vary with the age of the root and with the soil. Similar differences have been measured in opium poppies and foxgloves.

Understanding a pathway opens the possibility of building it somewhere else. Paclitaxel is now made partly by growing yew cells in large fermentation tanks rather than by stripping bark from trees. More ambitious projects have moved entire pathways into microbes. The route to vinblastine, an alkaloid from the Madagascar periwinkle used in cancer chemotherapy, involves more than thirty enzymatic steps, and in 2022 a team of researchers reported that yeast cells had been engineered to make the two compounds from which it is assembled, although the quantities produced were tiny. Yeast has also been modified to make artemisinic acid, a precursor of artemisinin.

Much remains unknown. Most plant species have never been examined chemically, and even in well-studied crops the regulation of these pathways is poorly understood: a plant may contain the genes for a compound and yet never make it. Biologists also argue about why plants produce so many similar compounds, some of which appear to have no function at all. For medicine, the practical question is whether engineered microbes and cell cultures will replace the field, or whether farmers will remain the first step in the production of plant-based drugs.

In 1995 a research institute in South Africa filed a patent on appetite-suppressing compounds extracted from a succulent plant of the Kalahari. The San, who had chewed the plant for generations to ward off hunger on long journeys, had not been consulted. The episode is often told as a simple story of theft and has become the standard example in arguments about what is usually called biopiracy. The real questions are harder: when a medicine is developed from knowledge held by a community, what is owed, and to whom? This article argues that protection is justified, though the instruments used to provide it are clumsy.

The case for protection rests on a simple observation. Traditional knowledge is not a free resource lying about for anyone to take; it is the product of long experiment, transmitted across generations, and it often points researchers towards plants they would otherwise never have tested. Screening plants at random is expensive and largely fruitless; knowledge narrows the search. If a company profits from that narrowing, the argument runs, the descendants of the people who did the work have a claim on part of the return. The Hoodia case also shows how difficult such a claim is to enforce. Under pressure, the institute and the San reached an agreement in 2003 giving the San a share of any royalties, but the company that had licensed the patent later abandoned the drug and the payments never materialised.

Critics raise several objections. Knowledge of plants is usually widely distributed, they point out, and it is often impossible to say which community holds it. A remedy may be known to many villages, recorded in a medieval text or sold in a city market; attributing it to a single group can be arbitrary, and may give one community a monopoly over something that others also use. Nor is the boundary of a community clear, since people marry out and move away. Traditional knowledge is the work of no identifiable author, which is precisely what makes it awkward for a legal system built on individual invention.

The history of particular drugs is less straightforward than campaigners suggest. The Madagascar periwinkle, source of the anticancer alkaloids vincristine and vinblastine, is routinely cited as an example of knowledge taken without payment. The plant had a place in local medicine as a remedy for diabetes, but its anticancer activity was discovered by chance in the 1950s, when researchers testing that claim in the laboratory noticed an unexpected effect on white blood cells. The periwinkle is a genuine case of a poor country's plant enriching a rich company, yet it is not a case of stolen knowledge, and the claim that it is has been repeated so often that it is rarely examined.

The law has tried to respond. The Convention on Biological Diversity, agreed at the Earth Summit in Rio de Janeiro in 1992, confirmed that states have sovereign rights over the genetic resources within their borders and that access to them should be granted on agreed terms. The Nagoya Protocol, adopted in 2010 and in force since 2014, went further, requiring users of genetic resources to obtain the consent of the provider country and to share the benefits. Yet the United States has signed the convention and never ratified it, and many countries have still not passed the domestic legislation the protocol requires.

Patents raise a separate problem. A patent should be granted only for something new and inventive, and a remedy described in an ancient text is neither. Yet patents have been granted for uses of plants that were long established: a patent on the use of turmeric for healing wounds, issued in the United States, was revoked in 1997 after a challenge, and a European patent on a neem-based fungicide was revoked after a long campaign. Challenging such patents is costly. India's response was to build a database, the Traditional Knowledge Digital Library, which translates old texts and makes them available to patent examiners. Defensive protection of this kind is cheap and effective.

Even where an agreement is reached, its value depends on its terms. A single payment at the start of a project is not an adequate substitute for a long-term stake: it transfers all the risk to the community, which may have identified a plant that never becomes a product. A small royalty on sales, by contrast, links the community's income to the success of the product and costs the company nothing if the project fails. Agreements should also include funding for research capacity in the source country, so that local scientists take part in the work instead of simply handing over samples.

What would a better system look like? The first step is documentation: recording remedies in databases that patent offices can search, so that bad patents are refused before they are granted. The second is a model contract, one that guarantees a continuing royalty, requires the consent of the community concerned and provides for training in the source country. The third is honesty about outcomes. Only a small fraction of traditional remedies will ever yield a drug, and promising cures to villages in exchange for access to their plants raises expectations that cannot be met. Much of the value of the knowledge lies in guiding research, not in the remedies themselves.

None of this makes the protection of traditional knowledge a simple matter of justice. The strongest argument is not that a community owns a molecule, but that it should share in the gains made from it, and that a system allowing those gains to be taken without consent will eventually destroy the knowledge itself. Protection is justified, above all, as a matter of fairness, and as a safeguard against patents that should never have been granted. Both are reasons of principle, and neither requires us to pretend that a village owns a chemical formula.