I don’t know a more accurate biomarker for prenatal androgen that can be readily measured in adults.Marc Breedlove, Michigan State University
我不知道更準確的產前雄激素生物標誌物，可以在成人中輕鬆測量。
我不知道可以在成人中輕鬆測量出比"產前雄激素"更準確的生物標誌物
密歇根州立大學Marc Breedlove
STEPHAN SCHMITZ/FOLIO ART
Talk to the hand. Scientists try to debunk idea that finger length can reveal personality and health
By Mitch LeslieJun. 6, 2019 , 8:00 AM
If papers published in the past 6 months are right, a single number is enough to show whether people are likely to suffer a premature heart attack, land first authorship on published papers, become dependent on alcohol, or put on fat around the middle. That magic number is the ratio between the lengths of the second and fourth fingers, known as the 2D:4D ratio. It tends to be lower in men—meaning their fourth fingers tend to be longer than their second—than in women. Researchers who believe in its predictive power say it reflects a fetus's exposure to testosterone and other hormones that guide development, including that of the brain.
The idea that the lengths of human fingers reveal so much stems from the work of evolutionary biologist John Manning, now at Swansea University in the United Kingdom. But the field he inspired has ballooned beyond what he could have imagined. More than 1400 papers in just over 20 years have linked the finger ratio to attributes such as personality, cognitive abilities, and sexual orientation as well as to risk of illnesses such as cardiovascular disease, cancer, and amyotrophic lateral sclerosis. Researchers have even tried to use ratios gleaned from stenciled handprints on cave walls to determine whether the artists behind ancient paintings were men or women.
But the notion has also riled plenty of critics, who argue that researchers who rely on the 2D:4D comparison have been seduced by a simplistic, faulty measure. Some doubters contend that the difference in ratios between the sexes is an illusion resulting from men's larger hands or that the measure itself is statistically problematic. "I'm skeptical about every single finding involving that ratio," says physiologist and biostatistician Douglas Curran-Everett of National Jewish Health in Denver.
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Other detractors argue the field is rife with irreproducible findings. It's "like a house of cards built on an unknown and uncertain base," says psychologist Martin Voracek of the University of Vienna, who compares the work on finger ratios to phrenology or physiognomy, the discredited ideas that people's head shape or facial features, respectively, reveal their personalities, character, and intelligence.
Yet as a simple, easy-to-measure quantity that promises insight into a hidden time of life—early fetal development—the finger ratio has enticed an entire generation of researchers while dismaying many others. To behavioral neuroendocrinologist Kim Wallen of Emory University in Atlanta, a skeptic, the debate over the ratio and its significance "raises some fundamental issues about what we consider evidence."
Forecasting with fingers
A German anatomist first reported in the 1870s that finger proportions typically differ between the sexes, but the observation remained a curiosity until Manning hauled the ratio into the spotlight in 1998. He was collaborating with colleagues at a fertility clinic in Liverpool, U.K., studying symmetry in the body, which some researchers suspected was connected to hormone levels. "I had a vague recollection that I'd heard about that sex difference" in finger ratios, Manning says. The disparity suggested a role for certain sex-related hormones. When he and colleagues measured finger ratios for patients at the clinic, lower ratios in men's right hands correlated with higher testosterone levels.
The long and short of it
John Manning and colleagues' 1998 study comparing the lengths of index (2D) and ring (4D) fingers found a subtle difference between the sexes, which they and others attributed to hormones affecting early fetal development.
2D4D0.80.911.11.21.31.4001020203040405060Womenmean: 1Right 2D:4DCount0.80.911.11.21.31.4103050Menmean: 0.98Right 2D:4DCountFinger measurements were taken from crease to tip.
(GRAPHS) J. T. MANNING ET AL., HUMAN REPRODUCTION, VOL. 13, 3000, 1998; (ILLUSTRATION) V. ALTOUNIAN/SCIENCE
By studying children and young adults from the Liverpool area, the scientists also discovered that the finger ratio discrepancy between the sexes held for kids as young as 2 years. That finding led the researchers to postulate that the difference arose before birth and reflected hormone levels in the womb. The finger ratio, Manning explains, indicates the relative levels of testosterone and estrogen during early development.
Manning, who has written two books and more than 60 papers on the ratio, didn't expect that his findings would have such an impact. But the measure caught on. The idea that one number reveals so much about us is irresistible, notes statistical geneticist David Evans of the University of Queensland in Brisbane, Australia, who has studied the genetic basis of finger ratios. "Whenever you give a talk on the 2D:4D ratio, as soon as you mention it, everyone starts looking at their hands."
Researchers have used scanners, photocopiers, calipers, rulers, and even x-ray machines to assess finger length; in some studies the subjects measured themselves. Scientists can swiftly and cheaply amass large amounts of data. One BBC-sponsored online survey on sex differences gleaned self-reported finger ratios for more than 240,000 people. "I don't know a more accurate biomarker for prenatal androgen that can be readily measured in adults," says neuroscientist Marc Breedlove of Michigan State University in East Lansing.
Finger ratios also appeared to meet a scientific need. In the late 1950s, researchers proposed a then-radical idea—that testosterone and related sex hormones in the womb steer the brain's development and thereby shape adult behavior. Since then, scientists have sought links between prenatal hormone exposure and characteristics such as aggressiveness, sexual orientation, and spatial ability—along with the risk of conditions such as autism and addiction. But sampling hormones in an early fetus can endanger a pregnancy. No wonder researchers turned to the finger ratio as a simple readout of an otherwise inaccessible environment.
The studies build on subtle differences. Although the finger ratio is usually smaller in men, the gap between the sexes is small. In the BBC internet study, average right-hand values for men and women were 0.984 and 0.994, respectively. Moreover, the distributions for the two sexes overlap, and the average ratios vary widely depending on subjects' geographical origins and ethnic backgrounds.
Nonetheless, many scientists are convinced that the 2D:4D ratio is a reliable indicator. "I think there is no longer any doubt that these ratios in humans reflect prenatal androgen exposure," Breedlove says. Biological anthropologist Bernhard Fink of the University of Göttingen in Germany, another champion of the ratio, adds that hundreds of studies have shown that it correlates with a variety of behaviors and abilities that can plausibly be connected to prenatal androgens. However, he acknowledges that the ratio typically explains just a "small to moderate" amount of the variation in any particular trait.
I don’t know a more accurate biomarker for prenatal androgen that can be readily measured in adults.Marc Breedlove, Michigan State University
One high-profile use of the finger ratio has been to examine sexual orientation in women. Researchers have suggested that hormone levels early in development influence which sex people find attractive and that higher levels of testosterone and other androgens circulating through a female fetus might increase the odds of her being a lesbian. The hypothesis has been contentious and hard to test. Breedlove and colleagues thought finger ratios might yield new evidence, so in the early 2000s at street fairs in the San Francisco Bay Area in California, they "began asking people questions and Xeroxing their hands."
Although a difference in digit proportions was not evident between gay and straight men, the researchers determined that women who described themselves as lesbians had lower, more "masculine" finger ratios than did straight women. The unmistakable conclusion from that study and follow-ups, Breedlove says, is that "Testosterone does have an influence on human sexual orientation before birth."
Even among proponents of the finger ratio, however, those results didn't settle the controversy about prenatal hormones and sexual orientation. Manning, for instance, argues that the BBC study shows the opposite relationship—that early testosterone exposure is important for sexual orientation in men but not women.
Manning says the ratio also gives a glimpse of a person's future. For example, he says, finger ratios might forecast the effectiveness of prostate cancer treatments that block testosterone and of breast cancer treatments that block estrogen. "It's early days for this kind of thing," Manning says, but "we won't know until we do the studies."
The ratio's prognostic power is even stronger for sports, he says. Studies have uncovered associations between lower 2D:4D ratios and better performance in an array of athletic events, including soccer, long-distance running, rugby, skiing, rowing, and basketball. The effect is large enough, Manning contends, that teams should use finger ratio as a criterion for selecting players, "if we can get sports scientists to agree."
Digital problems
Yet the ratio has met with continuing skepticism from scientists. Unable to safely sample blood from early fetuses, researchers haven't confirmed the ratio's fundamental assumption: that variation in lengths of the key digits correlates with differences in hormone levels in the fetus's blood during the first trimester of pregnancy, when fingers begin to form. Instead, scientists have turned to indirect evidence. The strongest support, Manning says, comes from animal studies that involved tweaking the hormone environment during pregnancy.
[It's] like a house of cards built on an unknown and uncertain base.Martin Voracek, University of Vienna
In one study, developmental biologist Martin Cohn of the University of Florida in Gainesville and his then-postdoc, Zhengui "Patrick" Zheng, altered the activity of the receptors that respond to the hormones. For example, the pair stimulated the androgen receptor by dosing pregnant female mice with dihydrotestosterone (DHT), the most common form of testosterone in the body, or gave them estrogen to prod its receptor. Three weeks after the females gave birth, the researchers measured the effects of their manipulations on the hind paws of the pups.
In female pups, they reported in a 2011 paper in the Proceedings of the National Academy of Sciences, boosting the activity of the androgen receptor in the mother increased the growth of the fourth digit and produced a lower 2D:4D ratio. Nudging the estrogen receptor, in contrast, curbed elongation of the fourth digit and yielded a higher 2D:4D ratio in male offspring.
"The sex hormones can tap into the genetic circuit that controls skeletal growth," Cohn concludes. And because "the mechanisms that control limb development in all vertebrates are very, very conserved," he says, the hormones probably act similarly in people.
But the results of another animal study contradict those findings. When neurobiologist Sabine Huber, now at the University of Münster in Germany, and colleagues tried to replicate Zheng and Cohn's study, they got the opposite results. Boosting DHT levels in pregnant mice induced higher, more feminine digit ratios in the hind paws of male pups, whereas blocking the androgen receptor led to lower, more masculine ratios in female pups. Huber says she's not sure why those results, reported in PLOS ONE in 2017, don't match those of the other study, but she says differences between the strains of mice she and Cohn's team used may have contributed.
Inconclusive results from two large studies that scanned the genome for gene variants linked to finger length also raise doubts about the 2D:4D ratio, critics say. Evans and his colleague Sarah Medland, a statistical geneticist at QIMR Berghofer Medical Research Institute in Brisbane, analyzed data on thousands of people, looking for a relationship between the ratio and variants in the molecular pathways that control testosterone levels or responsiveness to the hormone. They came up empty. In two studies, "We didn't find any strong evidence of testosterone involvement," Medland says.
I just don’t think that finger ratios are a scientifically reliable measure of the early hormone environment.Melissa Hines, University of Cambridge
Skeptics suggest the 2D:4D ratio may be statistically meaningless. Ratios are intrinsically problematic, some statisticians say, because they can muddle the relationship between two variables. "A conclusion based on a ratio is likely to be off-target and misleading," says Gary Packard, a professor emeritus of biology from Colorado State University in Fort Collins, who has written extensively about pitfalls of statistics.
Before researchers use a ratio, Curran-Everett says, they should check that it meets certain mathematical criteria: A plot of its two variables should yield a line that passes through the origin, which indicates that the ratio's variables have a consistent relationship. But when evolutionary biologist Jaroslav Flegr of Charles University in Prague and colleagues performed that test in two studies of hundreds of finger length measurements, the 2D:4D ratio did not fulfill the criteria.
More sophisticated mathematical approaches to the data suggested the apparent difference in 2D:4D ratios between the sexes is merely a function of men's larger hands. Men may have longer fourth fingers because, as the hands get bigger, the fingers don't grow by the same amount—the fourth finger lengthens more than the second. In a 2017 study, Flegr and colleagues worked with researchers from Teesside University in Middlesbrough, U.K., to factor out the difference in hand sizes in their data. The male-female difference in digit ratios flipped—men now had higher values. That inversion suggests the widely reported sex difference in 2D:4D ratios is "not an effect of testosterone, it's an effect of the size of the hands," Flegr says.
That finding may help explain another problem that critics cite with 2D:4D studies: The results often can't be replicated. Melissa Hines, a psychologist and neuroscientist who studies human gender development at the University of Cambridge in the United Kingdom, once accepted the validity of the ratio. But she changed her mind when she asked some undergraduates to repeat published studies for their final-year projects. Even though students appeared to duplicate procedures from the studies, they couldn't obtain the same results.
"I'm not saying androgen is not at all important for human behavior. It is," she says. "I just don't think that finger ratios are a scientifically reliable measure of the early hormone environment." Wallen says the case that digit ratios are a proxy for hormone levels is so weak that when he became editor of the journal Hormones and Behavior 7 years ago, he decided to stop accepting papers that use them in that way.
Voracek, who like Hines once believed in the finger comparison, now says research on the 2D:4D ratio exemplifies the reproducibility crisis that has emerged in multiple fields of science over the past few years. Intriguing findings that appear in small studies disappear when scientists scrutinize larger groups or perform meta-analyses, he says.
Implementing some of the practices recommended for improving research credibility could help solidify the science and possibly bridge the gap between 2D:4D supporters and detractors, Voracek adds. Those measures include preregistered studies, in which investigators spell out their aims and methods before performing the work, and adversarial collaborations, in which scientists with clashing ideas team up.
But for now, skeptics and advocates of 2D:4D ratios seem to be talking past one another. Researchers who rely on the ratio aren't publishing their studies in Hormones and Behavior, but they are publishing. More than 20 papers using the digit ratio have already come out this year.
Posted in:
Biology
doi:10.1126/science.aay2735
Mitch Leslie
Science
Can our fingers forecast our personality and health?
Many studies—more than 1400—rely on the 2D:4D ratio, which looks at the lengths between our second and fourth fingers. But many scientists argue that the measure itself is statistically problematic.
SCIENCEMAG.ORG
Talk to the hand. Scientists try to debunk idea that finger length can reveal personality and health
STEPHAN SCHMITZ/FOLIO ART
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