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Are You Left-Handed? Science Still Yearns to Know Why

False leads and ever more complex hypotheses abound when scientists wonder why a minority of people are left-handed

Being left-handed can be devilishly hard. In 1937, an educational psychologist whose work was later discredited wrote of many left-handers that “they squint, they stammer, they shuffle and shamble, they flounder like seals out of water.” Beyond accusations of being gauche, left-handers have also had to deal with more sinister imputations. In fact, the Latin for “left” is sinister, and the left hand has historically been associated with witchcraft and devil worship. While the charges of being clumsy can often be attributed to left-handers having to put up with tools designed for right-handers, the connection to demonic powers is simply supernatural nonsense, though it is easy to imagine why left-handers—a small minority that gained invisibility as the world became more industrialized—were demonized for being different.

Once we put aside the bigotry, we are left with interesting questions. Why is it that a small subset of the population prefers to use their left hand for manual tasks, and why do we even show a preference in the first place? The body of research on these questions is a microcosm of the many challenges of doing scientific research and communicating it to the public. It’s a story of false leads, enduring myths, and hypotheses that become more and more complex as our understanding of genetics deepens.

Handing out imperfect surveys

What percentage of the population is left-handed? Sounds simple enough, but the devil is in the details. When researchers start to think about the question long enough, they realize it’s problematic. Questionnaires, like the Edinburgh Handedness Inventory, exist, sure, but some of their questions can rapidly become outdated. Ask a Millennial which hand they typically use to strike a match and you might be met with a confused face. Also, just because you write with your left hand does not mean you throw a ball with the same hand. This also brings up the issue of preference versus skill. You may prefer engaging in a manual task with your left hand, but in a test you may be revealed to be more skilled with your right hand. In fact, nearly a third of left-handed writers throw more accurately with their right hand (and a tiny percentage of right-handed writers throw best with their left).

Another kink to the story: when you ask Baby Boomers which hand they use to write, you might get deceptive numbers if your interest is in the underlying biology of handedness. That’s because for a good chunk of the twentieth century (and still in some cultures), it was common for schools to force the sinistral students to switch to the “correct” hand. Thus people born as left-handers were culturally forced to become right-handers. All of these problems have made it challenging to evaluate how common left-handedness is worldwide, with early estimates ranging from 1% to nearly 30%, but in 1994 the largest survey ever conducted and done in 32 countries provided the most reliable answer to date: 9.5%. Nearly 1 in 10 people worldwide reported using their left hand to write, with some variation from country to country. This was somewhat confirmed by an analysis of nearly 2.4 million individuals published last year which reported a range of 9.3% to 18.1% depending on how handedness had been measured.

Left-handed humans are thus in the minority, but it didn’t have to be this way. Marsupials who hop around on their hind legs, like the prototypical kangaroo, are actually more likely to prefer their left forelimb or arm. Other animals seem to show a preference for one wing or paw over the other, but this choice is inconsistent across or within species. In having a consistent preference for the right hand, humans are quite unique in the animal kingdom to the best of our knowledge.

Sinistral preference is shrouded in its own growing mythology. Studies published over the years have seemingly shown that more left-handed people than expected are diagnosed with a large number of diseases, from autoimmune conditions to psychiatric disorders. This led scientists to wonder if common biological pathways were involved. However, as a review paper by Brandler and Paracchini pointed out in 2014, these associations are much murkier than we’d like. Often they can be traced back to an unfortunate bit of publication bias. Whether or not someone is left-handed is a quick bonus question a researcher can throw into a survey. It doesn’t cost anything. If an association is found, it gets published because it’s novel. If none appears, it’s never mentioned. This is an example of bad science and not the only one as far as handedness is concerned.

You may have heard that, on average, left-handed people die seven years younger than right-handed people. This is not true. It comes from a poorly analyzed dataset derived from a baseball encyclopedia and published in the journal Nature in 1988. An equally flawed assessment published a few years later claimed the gap was nine years. According to Professor Chris McManus’ 2019 review on the myths surrounding left-handedness, a much bigger study done using the UK Biobank in more recent years showed no difference in mortality. Yet the myth persists, in part because of its wide coverage in the media, its shock value, and its memorability.

And it’s not the only myth about handedness that refuses to die. As researchers tried to get a handle on what causes our handedness, debunked theories went on to survive like sinister zombies.

Never simple, always complex

Scientists speculated on a number of causes for left-handedness: birth complications, the use of ultrasound scanning during pregnancy, even high levels of testosterone in the fetus, which were hypothesized to disrupt normal development of the nervous system. When fetal testosterone levels could finally be measured, no association was found with handedness. A 2015 Cochrane review found no significant link between the use of ultrasound and non-right-handedness, although some argue there could be an association in male babies. As for birth complications and other claims that left-handedness is only decided at or following birth, a series of papers (summarized here) have shown that most second- and third-trimester fetuses actually suck their right thumb, and that their thumb-sucking preference, left or right, predicts whether they will become left- or right-handed. It seems that left-handedness is usually set in stone before birth. Could the brain be responsible?

When Pierre Paul Broca began to pin down where language was being processed in the brain, he found an area, now named after him, in the left side or hemisphere of the brain. So the simplistic idea was that language was processed in the left half of the brain and it would make sense, for the purpose of efficiency, for writing skills to tap into this same half of the brain. Because muscle control is contralateral, meaning that control of your right hand is actually done by the left part of the brain, it was thought that this bit of brain wiring explained why most people were right-handed. Therefore, some sort of injury must cause a minority of people to shift their language processing skills to the right half of their brain, thus making them left-handed. However, we learned through a 1999 study that things were a bit more complicated than that. Using functional magnetic resonance imaging, a team of scientists found that when right-handers were asked to silently generate words, 4% of them showed activation of both halves of their brain. Meanwhile, when studying left-handers, only 10% of them showed right hemisphere activity for this task. The vast majority of them was processing language in the left half of the brain, like most right-handed individuals. Simplistic explanations have not survived scientific scrutiny, and genetics is no exception.

As the mysteries of the DNA double helix were unspooled over the course of decades, handedness researchers wondered if this new knowledge, ever more convoluted, might explain hand preference in humans. Handedness clearly had a genetic component: it could be at least partially inherited from our parents, and so-called identical twins (who are more or less genetically identical) were more likely to share hand preference than fraternal twins (who are essentially ordinary siblings born at the same time). So the easiest bet is that there is one gene that codes for hand preference. In its wild-type form, it would make us right-handed, but mutated it would turn handedness into a coin flip. This is a version of the simplest form of heritability, the “one gene, one disease” framework, exemplified by cystic fibrosis: there is one gene, CFTR, and when both copies are mutated, you get cystic fibrosis. (As it turns out, even this model is overly simplistic, as there might be other genetic factors that modify this risk.) Researchers investigated the X chromosome, where sex-specific traits are encoded, because left-handedness skews male: for every four women who are left-handed, we find five left-handed men. It’s not a vast difference, but it was different enough that scientists wondered if X marked the spot. No dice. The mystery of why more men than women are left-handed remains unsolved.

It turns out there is no single gene that codes for handedness. In the early 2000s, genome-wide association studies—which scan the entire genome of people with and without a particular trait to see if one group has changes in their DNA that the other group doesn’t and which might potentially be causing this trait—came back negative. There was no single, one-letter change in the DNA that could reliably be tied to left-handedness. Eventually, using massive data sets issued from the UK Biobank, the International Handedness Consortium, and the direct-to-consumer service 23andMe, a team performed the largest DNA analysis for left-handedness. They found not one, not two, but 41 spots in the DNA that were associated with the trait. Handedness, like asthma and height, turns out to be a polygenic trait: many genes are involved and each makes a tiny contribution.

However, this is not the end of the story. It turns out that it’s not just the DNA that matters, but also what’s sitting on top of it. Epigenetic marks can temporarily silence bits of DNA and are generally involved in regulating when DNA is active, and these marks may have an influence on handedness as well.

Scientists have only just begun to understand the complex underlying biology of this very basic trait, and shedding light on left-handedness can hopefully blow away the superstitious and damaging myths that have long tainted people’s perceptions of a trait that can actually be advantageous. If I’m a left-handed boxer (commonly known as a southpaw), I have the element of surprise on my side. While I’m used to fighting right-handed boxers because of how common they are, they are not used to fighting me. This surprise advantage has indeed been reported in many interactive sports, like fencing, tennis, baseball and martial arts, but not in non-interactive sports, like gymnastics and swimming.

The twist is that, if left-handedness were to become more common, its advantage in a match would diminish because right-handed athletes would encounter southpaws more frequently. This is known as a frequency-selection mechanism: in this case, left-handed people gain an advantage because of how rare they are. Indeed, as we move from amateur sports to the professional leagues, we see an excess of left-handers, where the advantage that helped carry them up to the top level may start to dry up.

We have come a long way from the days when the left hand was seen as the Devil’s hand and was tied to all manner of undesirable traits. The candle of science has helped to cast these beliefs back to the shadows, although we will need much more illumination before we can fully understand the intricate ways in which handedness emerges from human biology.

Take-home message:
-Counting how many people are left-handed is more difficult than it looks, because of variations in preference and skill from task to task and because of left-handers having been forced to write with their right hand, but the best estimate we have is that roughly 10% of the world population is left-handed.
-The claim that left-handed people die younger than their right-handed counterparts is not true and comes from flawed and highly publicized studies in the 1980s and 1990s.
-There is no one gene that determines if we are left- or right-handed; rather, dozens of bits of DNA seem to make small contributions to our handedness, and epigenetic marks, which regulate the expression of our DNA, may also play a role.


@CrackedScience

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