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No good parent wishes pain upon her child, but Verna Mahar wished it for two of her sons -- the eldest, Owen, most of all.

From the time he was a baby he was a roughhouser -- banging his head against walls and table corners without a whimper. When he was a toddler he'd bite his fingers to the bone unless she made him wear mittens indoors. His lips she could do nothing about: Owen chewed them happily until they bled.

"My husband and I didn't understand it. He didn't cry for nothing," Ms. Mahar said. "We couldn't understand why he wasn't feeling."

"Didn't it hurt?" she'd ask the growing boy. "No," Owen would say. "Well why not?" "I don't know, Ma."

Not until Owen was 3 -- the year he broke a bone in his foot and kept right on walking -- did the family from Bird Cove, Nfld., receive an explanation. Doctors told them their son had a rare and storied disorder -- a genetic condition that prevents the ability to perceive pain. He is normal in every other way, able to distinguish hot from cold and pat from pinprick; only the sensation of pain does not register.

The Newfoundland family is one of only 15 worldwide known to be affected by congenital indifference to pain, or CIP. But the curse of their inheritance could become a blessing for the rest of the world.

Scientists have found the mutant gene behind the bizarre condition and believe that mimicking its effects could lead to a new age of painkillers.

An international research effort led by Vancouver biotech firm Xenon Pharmaceuticals Inc. has confirmed that a single mutant gene is responsible for this rare pain disorder in nine families of different ethnicities in seven countries. Among them are the Mahars in Bird Cove, a 12-hour drive north from St. John's, where at least four members of three related families have been diagnosed, including Owen, now 20, and his brother Joshua, 11.

In a report to be published in the journal Clinical Genetics in April, the researchers list what patients have suffered without suffering -- double hip dislocations, lower-limb amputations, corneal abrasions, burns, stabs, gashes, head trauma and mutilating tongue-biting. A Swiss woman has experienced painless childbirth; one U.S. patient was able to undergo a cystoscopy, a painful exploratory bladder procedure, without anesthetic.

"It is somewhat surprising that one gene has such a profound effect," said study co-author Michael Hayden, co-founder of Xenon and a geneticist at the University of British Columbia. "This tells us that there is a primary target for pain perception that's most profound."

James Henry, a renowned neurophysiologist (not involved in the research) who has studied pain for 30 years, said the unexpected importance of this single gene marks a "monumental turning point in our understanding of pain."

Dr. Henry, scientific director of the Michael G. DeGroote Institute for Pain Research and Care at McMaster University in Hamilton, stressed that drug development is a long road. But for the 20 to 30 per cent of the world's population who suffer chronic pain, he said, "the discovery of this single gene may be a miracle if it can be translated into a new therapy."

To be affected with an indifference to pain, a child has to inherit two defective copies of the SCN9A gene -- one from each parent. Researchers say those who carry a single copy seem to have normal pain sensation and tolerance, which helps to explain the rarity of the disorder. Only in certain pockets of the world have carriers, often distantly related, come together to pass two copies to the next generation.

With so many families descending from small, remote founding populations, Newfoundland has long been a gene hunter's paradise, particularly places like Bird Cove. It hugs the Great Northern Peninsula, a tiny shoreline community where for generations the surnames have been as familiar as the rocks.

But the years have not been kind to Bird Cove with the closing of the cod fishery, and a population of 600 has dwindled to 250, with few jobs and no doctors.

It was to Corner Brook, about 400 kilometres south, that Ms. Mahar, a store clerk, and Mr. Mahar, a logger, sometimes went for medical help when Owen was younger. Elizabeth Ives, then clinical geneticist with Memorial University, first met them there in the mid-nineties. By then Dr. Ives, now retired, had already seen a boy from another Bird Cove family with indifference to pain.

After Owen's diagnosis, Ms. Mahar was told that she and her husband had a 25-per-cent chance of having another child affected; her youngest Joshua, was 10 months old when Dr. Ives examined him. (Their eldest son is unaffected.)

"He already had blisters on his hands that seemed to cause him no discomfort," Dr. Ives recalled.

As they began to compile the family tree of the Mahar family, Dr. Ives said, Ms. Mahar vaguely recalled an older cousin who had been afflicted. Dr. Ives said that cousin is now in his 30s and "had the worst time of all."

Decades before anyone understood CIP, his parents had been accused of child abuse, Dr. Ives said, as doctors demanded an explanation for his constant bone-breaking and bruises. That family, who have asked to not be identified, "went through the mill," she said.

Although CIP had since been recognized as a pervasive condition, Dr. Ives had to tell the Mahars a stark truth: "There is no specific treatment for this -- other than protection."

Dr. Hayden and geneticist Simon Pimstone, Xenon president and CEO, created the company more than seven years ago with a plan to learn the biological causes of common disorders by studying rare ones with opposite profiles.

Early on, for example, they identified two families in South Africa and Holland who suffer from a rare genetic disease that results in excessive bone growth. That has led to a drug in development to treat bone loss in osteoporosis.

Then, a few years ago, the Xenon team became interested in pain -- "probably the most ubiquitous disease in the world," Dr. Pimstone said. Yet treatments are often "fraught with liabilities." Morphine is highly addictive, while anti-inflammatories can wreak havoc on the gut and the heart.

The Vancouver firm was specifically interested in people who could feel no pain at all. Many disorders result in pain insensitivities, including leprosy and other conditions that leave patients unable to sweat or even sense when they have go to the bathroom. But an indifference to pain alone is much rarer.

Xenon researchers found the first known reference in a 1932 report that described a patient who made his living in the circus, performing a human pincushion act.

Since then, a relatively small number of case reports have popped up, often in small, obscure journals, which, while interesting, had little impact on the field of pain research, Dr. Hayden said.

Last December, researchers in England reported in the journal Nature the discovery of the pain-sensation gene in three related Pakistani families affected with CIP. They described a 10-year-old who impaled his own arms with knives and walked across burning coals as part of a street-theatre show. The boy died on his 14th birthday after jumping off the roof of a house. Other affected members of the family had lost parts of their lips and tongues after biting them.

Dr. Hayden said the paper on the Pakistani families begged the question: "Is this applicable to many populations? . . ."

By then, through networks of contacts, cold calls and anecdotal reports, the Xenon researchers had already gathered the DNA of CIP families from the United States, England, Switzerland, France, Italy, Argentina and Canada to answer the question.

When Owen Mahar heard about the young boy in Pakistan, childhood dares came back to him.

"They'd say, 'Oh he's tough and [egg]me on to doing different things," Owen said. " 'Do a cartwheel off the bridge,' they'd say. So I went and done it . . . Later my arm got rock hard . . ."

It was broken. In Grade 7, he broke his kneecap and a year later broke his leg playing basketball. "I just got up and continued playing."

To his parents' relief, Joshua has never been as rambunctious as Owen. But then, Ms. Mahar said, they've been more cautious with him: no hockey, no skiing. Instead, Joshua is a table-tennis fan and a volleyball player. "He's not had a broken bone," his mother said.

"He doesn't understand fully why he's like this," she said, "he just knows that he's different . . ."

The single gene behind the family's struggles suggests pain sensation is simpler than anyone thought.

"They are different mutations in different families, but it's all in the same gene [on chromosome 2]" Dr. Pimstone said. The defects are known as "nonsense" mutations that stop the SCN9A gene from working and producing a protein known as Nav 1.7. Previously, the gene has been implicated in extreme pain disorders and in conditions such as epilepsy and high blood pressure.

Both the protein and gene are already well known as belonging to a family of sodium-channel genes.

These channels, Dr. Henry said, are routes that allow pain signals to pass through the charged outer membranes of one nerve cell to the next. The channels, like gates, are normally closed. But they open for certain electrically charged signals and trigger a chain reaction.

Shutting off sodium channels is also well known to have analgesic effects, Dr. Henry said, noting that lidocaine, that dentist-office staple, blocks most or all of the known sodium channels. But it also leaves people numb and frozen, he said, making it no good as a general painkiller -- since people need to be able to feel something.

Dr. Pimstone said "it's like electricity that goes along a wire to provide light to a home." But at the moment, researchers cannot be sure exactly what role this wire plays and exactly where it blocks the light. "Certainly it is not the only gene implicated in pain."

Researchers have also been surprised that no other gene so far is known to compensate for such a profound deficit. As Dr. Ives put it: "Pain is one of the most fundamental protective devices that we have."

Since the gene was identified by Xenon, doctors have been able to screen for carriers in the Bird Cove area, Dr. Ives said. More than 50 have been tested, and at least 20 carriers have been found in the extended family.

Owen is blunt about the discovery his DNA helped produce: "It's good they got it for other people, but it does no good for me."

He believes that at some point during the past several years, his mother's wish came true: He thinks he began to feel painful sensations when he was around 11 or 12.

"When I was younger I didn't feel pain, it's true," he said. "But now I feel pain a whole lot. I have headaches all the time; my legs and hips bother me . . ."

His right leg is crooked from the breaks, twisted and pointing outwards and destroying his hips. He had surgery on his leg to try to straighten it, with 10 steel pins piercing his bones, which became infected. Now, he said, he can't persuade doctors to do much for him: "They think I don't know pain -- so they don't even believe me . . . unless I'm screeching or crying."

He'd like to have a hip replacement and painkillers. But he said the doctors take one look at his X-rays and conclude that a man with hip bones in such bad shape "shouldn't be able to walk at all," that it would be too painful to do so.

It's not the first time Dr. Ives has heard such things from people with CIP. "As these boys get older, they do describe feeling something, an awareness that something is not right, a discomfort."

It raises the question, she said, as to whether sensing pain can somehow be learned. Dr. Ives offered the story of the Bird Cove man with CIP, now in his 30s, who remembered feeling pain after breaking his leg in a car accident. Yet when researchers checked the hospital report of his emergency visit, she said, the doctors noted that he didn't seem to be in much pain at the time.

Dr. Henry said all this suggests some other mechanism may eventually compensate for the mutant gene. He noted that neuron-related shifts can take years to develop, as in Alzheimer's, which can start decades before symptoms appear.

There are only six or seven people left in Bird Cove who, like Owen Mahar, are in their 20s. "I would have been gone long ago as well if I could go," he said. But he can't stand much longer than a few minutes and he can't sleep. And now, it's Owen who has a wish.

"I wish I didn't feel pain any more."

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