May 16, 2000

On Left-Handedness, Its Causes and Costs

By DAVID E. ROSENBAUM

REDERICK, Md. -- In medieval times, right-handed warriors had a distinct advantage in swordfights. They held their shield with their left hand -- over their heart -- and thus lived to fight another day, and to reproduce, even after they had been stabbed.

That, suggested Thomas Carlyle, the 19th century British writer, is why so many more people are right-handed. The lefties never lived to have offspring.

It is a preposterous theory. Chances are, Carlyle, a brilliant essayist and himself left-handed, offered it tongue in cheek to tweak his contemporary Charles Darwin, whom he did not care for.

But the truth is, the question of what causes people to be right-handed or left-handed is nearly as much of a mystery today as it was when Carlyle addressed it in 1871.

The latest word comes from a geneticist at the National Cancer Institute laboratory here who has been working for years with yeast and mutant mice and who has developed a novel theory that he believes will explain why 9 out of 10 people are right-handed, why left-handed parents are more likely to have left-handed children and why identical twins often have different handedness.

The geneticist, Dr. Amar J. S. Klar, hypothesizes that most people have a specific dominant gene that makes them right-handed. But about 20 percent of people, under this theory, lack the right-handed gene, and these people without the gene have a 50-50 possibility -- a random chance -- of being right-handed or left-handed.

Whether a person has or lacks this gene, Dr. Klar supposes, is a function of conventional genetics, just like eye color or baldness.

The gene has yet to be identified -- assuming it exists. Dr. Klar is assembling a group of about 100 families that he plans to subject to genetic testing. If everything goes right, he said in an interview in his lab, he hopes to be able to prove his theory by isolating a right-handed gene, perhaps within three years.

Across the continent, at the University of British Columbia in Vancouver, Dr. Stanley Coren, a psychologist, has been working for years to document his view that left-handedness has nothing to do with genetic variables and almost everything to do with prenatal traumas -- with some sort of stress that damages the fetus.

Many researchers around the world do not take the all-or-nothing stands of Dr. Klar and Dr. Coren but hold that both genetics and development are involved. But what are the genetic elements? What are the developmental ones? There is no consensus.

The question of what causes handedness is interesting as a matter of curiosity and pure science. It is hard to think of another behavioral difference so observable and so fundamental that has not been explained.

But there is also a practical reason to want to know the answer. Left-handedness is closely identified with mental illnesses like schizophrenia and language difficulties like dyslexia and stuttering. If scientists knew the connection, they might be better able to deal with the problems.

"I'm not interested in handedness per se," Dr. Klar said. "I'm interested in how the brain works, and handedness is the only external feature we can monitor, because we can't look at the brain directly."

Born and reared in India, Dr. Klar, who is right-handed, came to this country to attend graduate school at the University of Wisconsin and did postdoctoral work at the University of California at Berkeley. Before going to the National Cancer Institute, he worked under Dr. James D. Watson (a lefty), the co-discoverer of the structure of DNA, at the Cold Spring Harbor laboratory on Long Island.

His studies of handedness, he said, began with his interest in the fact that yeast, single-cell organisms, have two distinct sides. His theory about the right-handed gene and the absence of this gene in lefties, he said, grew out of studies of mutant mice.

In most mice, the heart is on the left side. But there is a mutant strain of mice that have hearts on the right. When the mutants mate, half the offspring have hearts on the left and half on the right.

Last year, Dr. Klar said, geneticists identified a gene that is present in normal mice but totally missing in the mutants. "If it can work in mice," Dr. Klar asked, "why can't it work for handedness in people?"

The beauty of the theory is that it explains a phenomenon that has long baffled geneticists: how can identical twins with exactly the same genetic makeup have different handedness, as 18 percent of them do? Dr. Klar's explanation is that these twins lack the right-handed gene, and each one has an equal chance of being right-handed or left-handed.

He dismisses as inconclusive studies that militate against his genetic theory, showing that more men than women are left-handed and that left-handed mothers have a disproportionate number of left-handed sons. Possibly, he said, these findings can be explained by cultural factors like a tendency of left-handed males to be more stubborn than left-handed females in resisting efforts to switch them to using their right hands.

Hoping to prove his hypothesis, Dr. Klar plans to test blood samples or cheek swabs from the members of 100 families in which at least one parent is right-handed and two of the children are left-handed. "I'm looking for markers in their DNA to see how often these particular children inherit particular markers," he said.

He has a rigid definition of what constitutes right-handedness. He asks people which hand they use to throw a ball, use a spoon, saw, sew, shoot marbles, bowl, cut with a knife, cut with scissors, hammer and write. He does not consider people right-handed who routinely use their left hands for any of these activities.

As a research biologist who spends his life testing hypotheses, Dr. Klar said, he is all too familiar with going down blind alleys. But he said he was confident he would be able to isolate the right-handed gene.

Others experts wonder. One skeptic is Dr. Coren, the psychologist in British Columbia, who created a splash about a decade ago with his book, "The Left-Handed Syndrome" (Free Press, 1992), which maintains that lefties die younger and are more prone to accidents than right-handers. (Dr. Coren's avocation, incidentally, is writing about dogs, and he has published such page-turners as "How to Speak Dog" and "What Do Dogs Know?")

Dr. Coren is convinced that humans are naturally right-handed and that left-handedness is largely a consequence of what he calls "birth stress," by which he means factors like an unnatural placement that causes damage to the fetus in the womb.

Prenatal brain injuries explain why a larger percentage of left-handers have psychological and emotional problems, he said. He believes left-handedness runs in families because of a predisposition of the women in those families to have difficult pregnancies. As for the paradox of identical twins, he said twins are always subjected to birth stress because of crowding in the womb.

Two other scientists who have studied handedness -- Dr. Walter F. McKeever, a psychologist at the University of Toledo in Ohio, and Dr. Daniel H. Geschwind, a neurologist at the University of California at Los Angeles -- said they believed that handedness was heavily based in genetics. But they said they doubted a single gene was responsible, as Dr. Klar suggests. And they give more weight than Dr. Klar to developmental factors.

"Handedness is a complex behavior," Dr. Geschwind said, "and no complex behavior has ever been shown to be due to only a single gene without any environmental influence."

But Dr. Klar is undaunted. "What's good for yeast should be good for mice, and what's good for mice should be good for men," he said. "Biology is biology, and DNA is DNA."