THEY paraded down the streets two by two, each one鈥檚 beaming face a near-perfect duplicate of their partner鈥檚. More than 2000 twins and thousands of gawking spectators attended this year鈥檚 Twins Days, the largest gathering of its kind in the world, held every August in Twinsburg, Ohio. The town hit on this tourist-grabbing gimmick 27 years ago to celebrate its own namesake twins 鈥� the long-dead Wilcox brothers, who married sisters and died of the same cause on the same day. This year, like other years, twins came from near and far to show off their similarity, from little girls dressed as same-flavour sticks of gum to grizzled doppelgangers on a bicycle built for two.
And where groups of twins go, medical researchers follow. At the end of the parade, the twins filed into an area crowded with tents holding food, entertainment 鈥� and scientists. Some of the research booths offered frisbees and key rings; some even offered cash. Whatever the inducement, the twins were eager to participate, and long queues snaked in and out of the research tent. Ten teams had set up stalls to sign up volunteers for twin studies, the classic way of investigating whether a particular medical or psychological trait is determined by nature or nurture.
It鈥檚 a research tool that is enjoying a burst of popularity. Now twin studies are being used to calculate the heritability of everything from breast cancer to right-wing political views. Last year, for example, researchers at St Thomas鈥� Hospital in London declared that a key aspect of musical ability, pitch perception, was 76 per cent down to our genes. Journalists drew the conclusion that for some kids, music lessons were a waste of time.
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A sign of the field鈥檚 popularity is the existence of some 20 major twin registers worldwide, including one with 150,000 twin-pairs, as well as dozens of smaller groups of twins with specific diseases. In March the European Commission and other bodies awarded an 鈧�18 million grant to combine seven European twin groups into a 600,000-pair mega-register, for studying obesity, stroke and migraine, among other diseases.
But not everyone is so enthusiastic about twin studies and some people are downright hostile. Critics claim that the whole nature-nurture debate is wrong-headed 鈥� prompted by people who want to prove that social inequalities are down to our genes, not our culture. And they challenge it on more fundamental grounds too. To ask whether a feature is down to nature or nurture is meaningless, they argue, as nearly every trait you care to mention is affected by both. Are twin studies, a late 19th-century invention, sophisticated enough to investigate such complex interactions in the era of molecular biology and the Human Genome Project?
After all, the classic twin study design is very basic. Researchers look at two groups: identical (or monozygotic) twins, who come from the same fertilised egg and share all their genes, and fraternal (or dizygotic) twins who come from two different eggs and sperm and share half their genes. The twins are tested in different ways depending on the study. If the identical twins are more similar than the fraternal ones, the researchers conclude that heredity plays a role, the magnitude of which they can estimate.
Nazi experiments
The British scientist Francis Galton, the first to use the phrase 鈥渘ature and nurture鈥� in this context, helped pioneer twin studies more than a century ago. His research conveniently found that inherited intelligence lay behind the dominance of Britain鈥檚 upper classes, and took what we now see as a more sinister twist when he called for state-backed selective breeding programmes, to encourage talented people to proliferate like rabbits and dissuade lacklustre individuals from reproducing at all. It was the beginning of eugenics. The movement fell into disrepute when the Nazis became its biggest champion, and twin studies themselves became suspect as the Nazi scientist Josef Mengele tested his genetic theories on twins from concentration camps.
After the Second World War, London psychologist Cyril Burt studied several groups of separately raised identical twins and found that their IQs were highly similar, despite varying socio-economic backgrounds. Nature briefly claimed the upper hand in the nature-nurture debate 鈥� until the American psychologist Leon Kamin declared Burt鈥檚 work fraudulent. It turned out that no matter how many groups of twins Burt claimed to have studied, his figures for genetic influence remained exactly the same 鈥� a statistically highly unlikely result.
Kamin is still a steadfast critic of twin studies, even as other researchers have turned back to them. 鈥淭he consensus of the day is not so much a function of the 鈥榩ower鈥� of the studies, as of the prevailing ideology,鈥� says Kamin, who is now at the University of Cape Town in South Africa. Kamin is concerned that estimates of IQ heritability are used to influence public policy 鈥� to claim, for example, that education is wasted on people with low IQs. Others are uneasy with the personality and intelligence findings, unwilling to accept that these important drivers of personal destiny might be 鈥減re-programmed鈥�.
On scientific grounds, sceptics argue that twin researchers don鈥檛 assign family and social environment enough weight. They point out that while both fraternal and identical twins share the same environment, parents and other people are more likely to treat the identical twins as two halves of one person鈥� dressing them in the same clothes, for example. This means the heightened similarities seen in identical twins could be down to nurture after all, not nature.
鈥淚t鈥檚 unlikely that the twin method measures anything more than the greater environmental similarity of identical versus fraternal twins,鈥� says Jay Joseph, a psychologist at the La Familia Counseling Service in California and author of a forthcoming book, The Gene Illusion. Joseph cites a 1967 Norwegian study in which 90 per cent of identical twins were found to have 鈥渋dentity confusion鈥� in childhood, versus only 10 per cent of fraternal twins. 鈥淭here is little reason to accept that studies of twins measure anything more than environmental influences, error and bias,鈥� Joseph claims.
Womb-mates
Another criticism is that the similarities between identical twins might be caused by their shared environment in the womb, as well as their shared genes. The 鈥淏arker hypothesis鈥�, put forward in the 1980s, says that a pregnant woman鈥檚 diet 鈥渢eaches鈥� her child about what kind of environment to expect outside the womb, and so affects metabolism and later health. If a woman has a poor diet, for example, her unborn baby thinks times are tough, and is more prone to store calories as fat in later life. The theory developed because it was noticed that children with low birthweights were more likely to grow into overweight adults with diabetes and heart disease. The upshot for twin studies is that they could overestimate the impact of genes on these conditions.
But twin researchers defend their methods vigorously, on both ideological and scientific grounds. Identical twins often differ in birthweight and general health, yet still have similar rates of heart attack and diabetes, suggesting the Barker hypothesis is not all-important, they say. Given such prenatal differences, it鈥檚 remarkable that identical twins are as alike as they are, says Nancy Segal, director of the Twin Studies Center at California State University in Fullerton.
And when it comes to people鈥檚 tendency to treat identical twins identically, this could still be at least partly down to the siblings鈥� shared heritage. 鈥淧arents treat monozygotic twins more alike because the twins elicit more similar responses from them,鈥� Segal says. 鈥淚t鈥檚 not that the parents sit down and decide to treat them alike.鈥�
And consider all the cases of identical twins who have been reared apart and then reunited. While some may be overly eager to celebrate and emphasise their new-found twinhood 鈥� some have become media sensations 鈥� there is no denying that the hundreds of forks along their separate paths have been uncannily similar, despite their different upbringings. These cases suggest that it鈥檚 nature not nurture that makes identical twins so similar.
When it comes to ideology, twin study supporters argue that it鈥檚 old hat to regard this research model as a tool for people with dodgy political views. Robert Plomin of the Institute of Psychology in London says: 鈥淧eople worry about genetics but I don鈥檛 think genetics could ever do the damage that mother-blaming did in autism,鈥� referring to the now discredited 鈥渞efrigerator mother鈥� theory, which blamed the condition on bad parenting. Indeed, it鈥檚 thanks to twin studies that scientists now think autism is about 90 per cent genetically determined.
鈥淭win studies have been very important in changing people鈥檚 perceptions of the causes of human variation and setting more rational research and social agendas,鈥� says Nick Martin, director of genetic epidemiology at the Queensland Institute of Medical Research (QIMR) near Brisbane and editor of the journal Twin Research. 鈥淔or cases like autism, they have had a profound effect in resetting research agendas that were seriously off-course and removing the guilt feelings parents used to have.鈥�
And twin studies have been extraordinarily useful in allowing researchers to investigate diseases that would otherwise have been a genetic mystery. Single-gene disorders such as cystic fibrosis and sickle cell anaemia can be studied relatively easily, as they are passed on through simple Mendelian inheritance patterns. But more common disorders such as osteoporosis, obesity and manic depression develop when people inherit several 鈥渧ulnerability鈥� genes. Simple studies of ordinary families won鈥檛 reveal the extent to which genes are involved, as you can鈥檛 separate genetic effects from family environment. Identical twins, however, inherit all the same sets of genes, allowing twin studies to reveal the extent to which these complex diseases are genetically influenced. Plomin says: 鈥淯ntil you do these twin studies, your guess as to what is heritable and what is not isn鈥檛 worth very much.鈥�
The DNA dimension
Just because new molecular techniques to study genetics have arrived on the scene, that doesn鈥檛 mean twin studies are behind the times. In fact, they are proving more powerful than ever. Researchers can now use new forms of twin studies to learn the precise mechanisms that lie behind individual differences. 鈥淭he stuff we鈥檙e doing now involves looking at the DNA in more detail,鈥� says Tim Spector, director of twin research at St Thomas鈥� Hospital in London, which has Britain鈥檚 largest medical register of twins. 鈥淚t鈥檚 going to the next layer of complexity. You might need only two or three pairs to do it, whereas with normal people you might need hundreds or thousands of people.鈥�
One technique investigates identical twins who differ in a particular trait or disease, using sophisticated DNA array technologies, which can quickly and efficiently test thousands of genes. Researchers look at disparities in the twins鈥� gene expression, hoping to turn up an environmental trigger or a single new mutation that caused the condition. It is proving an enormously powerful tool to investigate every gene being expressed in a particular tissue in just a single pair of twins when only one has a certain disease. Last month, for example, Jeff Murray at the University of Iowa discovered one of the genetic causes of cleft lip by studying a pair of identical twins, one with the condition, one without (快猫短视频, 7 September, p 16).
Another method is to study identical twins who have different lifestyles. Five years ago Spector鈥檚 team showed that if an identical twin smoked while their sibling didn鈥檛, the smoker鈥檚 face became more wrinkled as they aged. Doctors have known for some time that smoking is bad for the skin, but looking at two twins side-by-side, one of whom is significantly craggier than the other, certainly rams the message home.
Applying molecular biology techniques to twin research can even shed light on one of the murkiest areas of genetics. Critics of twin studies sometimes claim it is meaningless to estimate the heritability of any particular trait, because this value isn鈥檛 always fixed 鈥� it can depend on the environment in which someone is brought up, as well as the presence or absence of other genes.
For example, variation in obesity is reckoned to be about 70 per cent down to our genes, and 30 per cent environment. But in areas where humans can barely scratch a living, they could be much more likely to be skinny, whatever their genes. In this case, the environmental contribution would be higher than 30 per cent. And someone with an unusual genetic mutation might never be fat, no matter how much they eat 鈥� with them, the environmental contribution would be less.
But twin researchers reply that useful generalisations can still be made about the heritability of most traits, given the average environment of a defined population and its typical genetic background. And twins are emerging as the ideal tool for probing these complex gene-environment interactions.
The reason is that without twins, it鈥檚 hard to separate the effects of 鈥渘ormal鈥� genes that directly affect the level of a trait (like weight or blood pressure), from 鈥渆nvironmental sensitivity genes鈥� that modify how sensitive the trait is to external influence. Identical twins nearly always share all their genes, so when one is fatter than the other, it must be down to environmental effects alone. So researchers can screen their databases for several identical-twin pairs with 鈥渄iscordant鈥� weights. If certain versions (or 鈥渁lleles鈥�) of gene X are linked with high or low discordancy for weight, you鈥檝e found your smoking gun.
Research into such environmental-sensitivity genes is only just starting to take off, but Martin at the QIMR believes that they could be more important than 鈥渘ormal鈥� genes as a cause of disease, and so could be highly medically significant. That鈥檚 because environmental sensitivity genes are more likely to push the degree of a physical trait to extremes, he says.
One of the first known examples of this phenomenon is the relationship between cholesterol levels and M/N blood groups 鈥� a different classification from the better-known A/B/O system. Martin鈥檚 team showed through twin studies that people in blood group N have much more variable cholesterol levels than those who are M. Though the exact reasons for this are unclear, the researchers hit on a practical consequence. For N-group people, switching to a low-fat diet 鈥� changing their environment, in other words 鈥� was more effective at cutting blood cholesterol levels than with M-group people.
Such molecular detective work seems light years from Galton鈥檚 classic twin study. But who knows if and when all the mysteries will be solved? As one pair of young guinea pigs settled down with Twinsburg researchers studying differences in the sense of taste, their mother, Joanie Cuff from Buffalo, New York, laughed as she watched them down vials of liquid and make faces. Until a DNA swab at Twinsburg three years ago showed that her twins were identical, she had thought they were fraternal. 鈥淥ne is a perfectionist, one can鈥檛 be bothered,鈥� Cuff said. 鈥淥ne studies hard and one just blows her schoolwork off. But still they get the same results on their tests.鈥� Now who can explain that?
