IELTS Academic Reading Practice Test 394

Every year, blood from several million newborn babies is allowed to dry on a small card and sent to a laboratory. The sample is taken by pricking the baby's heel and squeezing a few drops onto the card, which is then left to dry at room temperature. From that single sample, laboratories can tell whether a baby is at risk of a rare but serious disorder. The cards are commonly known as Guthrie cards, after the American physician and microbiologist Robert Guthrie, who devised the first practical test of this kind.

The disorder that started it all was phenylketonuria, or PKU. In 1934 a Norwegian physician, Asbjørn Følling, was consulted by a mother whose two children were severely disabled. Testing their urine, he found a substance that is not normally present, phenylpyruvic acid. Følling had identified a condition in which the body cannot break down phenylalanine, one of the amino acids that make up ordinary dietary protein. Because the amino acid is not processed, it accumulates in the blood and damages the developing brain. PKU is now known to affect roughly one baby in every 10,000 to 15,000.

For nearly two decades there was nothing that could be done. That changed in 1953, when Horst Bickel, a German-born paediatrician working in Birmingham, England, showed that a diet low in phenylalanine could prevent the damage. The diet is demanding, but for a child who escapes the neurological effects it is transformative. Its usefulness, however, depended entirely on timing. If it was begun in the first few weeks of life, before symptoms appeared, the brain developed normally; once the harm had been done, it could not be reversed. In the mid-1950s most affected children were not identified until their parents noticed that something was wrong, by which time it was far too late.

Robert Guthrie was born in 1916 in Marionville, Missouri, and trained in medicine and microbiology. He worked for several years as a research physician at the Roswell Park Memorial Institute in Buffalo, New York, before moving in 1958 to the medical school of the University at Buffalo, where he became professor of paediatrics and microbiology. He found the situation intolerable: a treatment existed, but the babies who needed it were being found too late to benefit from it.

Guthrie's solution came from microbiology. The growth of certain bacteria is inhibited by chemical relatives of naturally occurring compounds, and the inhibition is reversed if the natural compound is present. Working with Bacillus subtilis and a substance called beta-2-thienylalanine, which blocks the bacterium's growth, he built an assay in which the amount of phenylalanine in a blood sample determines how well the bacteria grow. A disc punched from a dried blood spot is placed on a dish of agar containing the inhibitor. If the blood contains excess phenylalanine, the amino acid neutralises the inhibitor around the disc and the bacteria grow in a ring. The diameter of that ring indicates the concentration, and the plates are read after incubation overnight.

The other half of Guthrie's achievement was logistical. Blood had been collected on filter paper before, but he turned the practice into a system that could reach an entire population. Thick absorbent paper of a type already used in laboratories absorbed a few drops evenly, dried quickly and needed no refrigeration. Cards could be stacked, labelled and sent by ordinary post from a clinic or a family home to a central laboratory, and the assay itself required nothing more elaborate than an incubator and a supply of agar plates. A midwife visiting a family could take the sample, and the result would be available within days.

In 1963 Massachusetts became the first state to require that every newborn baby be tested for PKU, using Guthrie's method. Other states followed at their own pace over the next few years, and so did health services in other countries. Guthrie travelled widely to promote the idea, carrying samples with him and helping laboratories to set up the test, and he developed similar assays for other inherited metabolic disorders, including galactosemia and maple syrup urine disease.

Screening for PKU therefore became a test case for a much broader principle: that a drop of blood taken from every baby could prevent permanent disability. The principle was extended gradually to other conditions, and by the 1980s programmes in several countries covered a handful of disorders rather than one. Each addition required its own method, its own evidence and its own argument with health departments, and progress was slow.

The bacterial assay itself has since disappeared from laboratories. Through the 1980s and 1990s it was replaced by automated methods, and from the late 1990s tandem mass spectrometry made it possible to measure dozens of metabolites in a single analysis. What has not changed is the beginning of the process: a heel prick, a few drops of blood and a card that still bears Guthrie's name. He died in 1995, by which time screening for PKU had become routine in much of the world.

The significance of the work is easy to overlook. PKU is rare and the diet is burdensome, but children who are identified in time and treated grow up without the intellectual disability that the condition once caused. Multiplied by the millions of babies tested each year, the result is one of the most effective preventive measures in public health, achieved in the first instance with a bacterium, a dish of agar and a piece of absorbent paper.

Newborn blood-spot screening is one of the quiet successes of modern medicine. A few days after birth, a midwife or nurse warms the baby's heel, pricks it with a sterile lancet and fills a series of printed circles on a card with blood. The card is dried, given an identifying number and sent to a regional laboratory. From that sample, a laboratory can check for several dozen rare conditions, most of which would otherwise become apparent only when a child failed to thrive or became seriously ill.

Timing matters. In the United Kingdom the sample is normally taken on the fifth day after birth, and most other programmes collect it within the first week. The delay is deliberate. Some of the substances being measured change sharply in the first hours of life, and a sample taken before feeding is established may give a misleading result. Babies who go home very soon after birth sometimes have their sample taken too early, and a second card is then needed. A blood transfusion is another complication, because transfused cells can mask the very abnormality the laboratory is looking for.

Different conditions require different measurements. Congenital hypothyroidism, in which the thyroid gland fails to develop properly, is detected by measuring the level of thyroid-stimulating hormone. Phenylketonuria is found by measuring phenylalanine. Cystic fibrosis is picked up indirectly, through a substance called immunoreactive trypsinogen, which is raised in many affected babies. Sickle cell disease and related haemoglobin disorders are identified by examining the haemoglobin itself, using a technique that separates the different forms of the protein. A single card therefore passes through several different analytical processes.

The most powerful of these processes is tandem mass spectrometry, which arrived in newborn screening in the late 1990s. A punch removes a small disc from the dried blood spot, and solvents extract the compounds it contains. The sample is then vaporised and given an electric charge, and the resulting ions are separated in two stages according to their mass and their charge. In a single run lasting a couple of minutes the instrument can measure dozens of amino acids and fatty-acid compounds. That capability is why screening panels expanded so quickly once the technology became available.

None of these tests is a diagnosis. A screening test is designed to sort a very large number of babies into a small group who need further investigation. For each condition the laboratory uses a cut-off, a level above or below which the result is treated as positive. Because the aim is to miss as few affected babies as possible, cut-offs are set cautiously. As a result, most of the babies who are recalled turn out to be healthy. A raised trypsinogen level, for example, has many causes other than cystic fibrosis, and the diagnosis is confirmed by a sweat test that measures the saltiness of a baby's sweat.

The recall itself has a cost. Parents who are telephoned a week after the birth and told that their baby needs more tests often describe acute anxiety, and the interval before the second result arrives can be miserable. This distress is, in a sense, the price of finding the few. Programmes try to reduce it with clear information and rapid follow-up, but they cannot eliminate it, and the balance between missed cases and unnecessary alarm is one of the recurring arguments in the field.

A second difficulty is that some findings are ambiguous. A result may show that a baby carries a genetic variant associated with a condition without necessarily causing it, and nobody can say at that point how the child will be affected. In some conditions the range of severity is wide, from mild forms that need little treatment to severe forms that need a great deal, and a screening result cannot distinguish between them. Parents may then be given a label without a prognosis, and clinicians must decide how closely to monitor a child who may never become ill.

Behind the scenes, programmes invest heavily in quality control. Laboratories analyse panels of samples with known values to check that their instruments are performing as expected, and they exchange samples with other laboratories so that results can be compared. Speed matters as much as accuracy. Treatment for congenital hypothyroidism should begin within a few weeks of birth if the brain is to develop normally, so samples must reach the laboratory, be analysed and be reported without delay, and a postal strike or a public holiday can become a clinical problem.

The cards themselves are usually kept after testing. Some programmes store them for months, others for decades, and stored spots have proved valuable for research, for auditing the performance of a programme and occasionally for investigating a child's death. Storage also raises questions about privacy: the spots contain DNA, and parents are not always told how long the card will be kept or who may have access to it. Most programmes now publish a policy and allow parents to ask for the card to be destroyed.

The next stage is likely to be genetic. Several countries are studying whether whole-genome sequencing should be added to, or eventually replace, the current tests. Sequencing would find far more than a panel of biochemical markers, but it would also produce findings of uncertain meaning and, potentially, information about conditions that would not affect the child for decades. How much of that information should be returned to parents, and when, is a question that laboratories are only beginning to answer.

When newborn screening began, it looked for a single condition. Panels in most high-income countries now cover anything from a handful of disorders to several dozen, and the technology exists to test for far more. Whether programmes should keep expanding is one of the more consequential questions in public health, because the answer determines what millions of families are told about their apparently healthy babies.

The framework most often invoked dates from 1968, when two public health doctors, James Wilson and Gunnar Jungner, prepared a set of principles for the World Health Organization. They listed ten conditions that a screening programme ought to satisfy. The condition should be an important health problem; its natural history should be understood; there should be an accepted treatment; there should be a test that the population will accept; and the cost of finding cases should be economically balanced against the expenditure on care as a whole. The principles were written for screening in general, at a time when newborn testing was in its infancy, yet they remain the starting point for almost every subsequent discussion.

Expansion, however, has not always followed those principles. Tandem mass spectrometry, which can measure dozens of compounds from one blood spot, transformed what was technically possible in the 1990s. In the United States a report from the American College of Medical Genetics in 2005 recommended a single uniform panel in place of the existing patchwork of state programmes, and listed close to thirty conditions as core. The effect was to standardise screening across the country. Critics have observed that the panel grew largely because the instrument could do the work, rather than because evidence for each condition had been assembled first.

The case for expansion is not trivial. Rare diseases are individually uncommon but collectively numerous, and for a few of them early treatment prevents harm that cannot be undone later. Screening also ends what families call the diagnostic odyssey, the years of appointments and inconclusive tests that often precede a diagnosis of a rare disorder. Families of affected children argue, reasonably, that a name for the condition is valuable in itself: it brings access to specialist care, to other families and sometimes to research. For parents who learn that they carry a variant, there is also information about future pregnancies.

Against this must be set the harms that screening itself produces. A screening test is not a diagnosis, and every programme generates false positives. The families involved are usually told only that something may be wrong, and the days or weeks before the follow-up tests are completed can be extremely distressing. A programme cannot be judged by the number of cases it finds; what matters is how many children it helps, and at what cost in anxiety to the many who are needlessly recalled.

The harder problem is uncertainty. Genomic sequencing, which some programmes are now piloting, does not simply return a yes or no. It returns variants, many of which have never been seen before and whose significance nobody can state with confidence. A child may be given a label that predicts an illness that never arrives, with surveillance and anxiety as the consequence. Sequencing can also reveal that a child is a carrier of a condition that will never affect them, and may reveal predispositions to adult diseases; a consent given in the first days of life cannot bind the person the baby will become.

There is a further, less discussed objection. A screening programme is not a test; it is a system, and the test is the cheapest part of it. Diagnosis, specialist clinics, treatment, dietetic support and a data system that can trace every baby all have to be paid for. Where a condition is added without the clinical services to look after the children identified, the benefit is doubtful and the burden falls on families. In countries where treatment for an identified condition is unavailable, screening for it offers information without hope, and the resources might do more good elsewhere.

My own view is that the criterion should be benefit rather than knowledge. Where there is good evidence that early treatment changes the outcome, and where the health system can deliver that treatment, a condition should be added; the argument for detecting it is then straightforward. Where the evidence is uncertain, the right response is a research study with explicit consent, not a national programme. That is not a rejection of new technology. It is a demand that the technology be evaluated in the way any treatment would be.

Screening programmes have an unusual moral weight. They approach families who have not asked for anything and offer them information that may be frightening, useful or both. That asymmetry creates an obligation to be sure of the benefits and honest about the limits. The United Kingdom's National Screening Committee, which advises on each condition separately, has the right structure: it can and does reject tests for which the technology exists but the case has not been made.

The aim should not be the longest possible list. A short programme, well run, with rapid follow-up and funded clinical services, protects more children than an ambitious one that leaves families to find specialists for themselves. Guthrie's test succeeded because it was simple, cheap and attached to a treatment that worked. That combination, rather than the sophistication of the laboratory, is what should guide the next expansion.