Loneliest island may hold key to asthma

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'Loneliest island' may hold key to asthma

A gene hunter's adventure: Toronto researcher pins hopes on 'super-duper kibbutz' in South Atlantic

Sarah Scott, National Post
Saturday, January 18, 2003

 

There is something about the loneliest island in the world that Dr. Noe Zamel finds completely irresistible. Maybe it is the remote location: The island, Tristan da Cunha, sits in the middle of the South Atlantic, midway between South America and Africa. Or perhaps it is the people -- 300 or so residents, all cousins, who live there without most of the amenities of modern life, such as telephones and TV. They are very hospitable once you get to know them -- if you do get to know them, because the island is so inaccessible.

The island has no airport, no dock and only one telephone, which is manned by the island's administrator. It take a week to sail there aboard a ship from Cape Town, 10 days from Rio, and the trip is not likely to be very comfortable because of the mountainous seas, thick fog and wild winds. Research and fishing vessels only pass by the island every couple of months.

But Zamel, a Brazilian-born respirologist who works out of Toronto's Mount Sinai Hospital, has been drawn to the place ever since he was a medical research fellow in London, England, 40 years ago.

In fact, he has read every word printed about Tristan because of one peculiar feature of its inhabitants: Nearly half of them have asthma, far more than the rate in the North American population, which is 10% in children and 5% in adults.

Something about their genetic profile predisposes the Tristanians to asthma, a complicated disease caused by several genes interacting with each other and the environment.

Asthma starts as an allergic reaction and as the body's defensive system rushes to combat the perceived invader, it causes inflammation in the inner airways, with unpleasant effects: shortness of breath, wheezing and coughing.

 

Zamel is not a geneticist, but when he saw how many Tristanians have asthma, he thought they might help scientists locate the genes that promote asthma. Because they had intermarried for their 150 years on the issland, their genetic profiles would be so alike that the genetic differences that distinguish asthmatics from people without the disease might be detected.

So, a decade ago, he set off from Cape Town on a South African fishing vessel, the SA Agulhas, to begin the voyage of his life -- a hunt for genes that took him across treacherous seas to the island, and then into the high-stakes multi-million-dollar world of modern biotechnology, where he was suddenly thrust into a very modern debate about patenting human life.

The life of a gene hunter is one that Zamel clearly relishes. At 67, he is tanned and fit, nattily dressed in clothes that his wife, a travel agent, has chosen.

Zamel, the son of Polish Holocaust survivors, works out of a tiny office at Mount Sinai, in which he keeps lots of large pictures of Tristan to show visitors.

Zamel first learned about the Tristanians just after they had been evacuated from the island in 1961.

A small volcano had erupted near the Tristanians' settlement, a little tongue of flat land at the foot of a 2,000-metre extinct volcano that dominates the island.

They were shipped to England -- the island was a British territory -- and encountered for the first time big-city life in the 20th century.

It was traumatic. The British newspapers wanted to see how the Tristanians reacted to the 20th century, after a simple homespun life on the island. The scientists were equally intrigued by the inbred community, and performed 66 studies over 18 months on everything from the colour of their eyes to their fingerprints, nutritional habits and level of retardation.

Zamel worked on one of the studies, which confirmed that half of the islanders -- or Highlanders, as they call themselves -- had asthma, or "hashmere" as they pronounce it.

The Tristanians did not like the English life at all. After less than two years in England, they voted to go home. As soon as the island was deemed to be safe, they returned. The sign, "Welcome to the Loneliest Island," was still standing.

It would be a long time before Zamel renewed the Tristanians' acquaintance. Nearly 30 years later, the study of genetics had advanced to the point where Lap-Chee Tsui, a Toronto scientist, discovered in 1989 the gene that causes cystic fibrosis.

That spectacular find got Zamel thinking. Maybe if he collected blood from the Tristanians, the study of their DNA would reveal the gene or genes that promote asthma. In Zamel's words, "I said to myself, 'It's time to go for the genes of asthma.' "

Getting there was a different story. First, he had to transmit the request by sending a fax to Cape Town that the operator would read over the radio to the operator in Tristan.

The response from the islanders: No. They were sick of medical researchers who promised great things if they would participate in a study. They refused again and again until Zamel finally made a videotape in which he showed his face and how the blood tests would be done.

They finally said yes. "They were moved," he says, "because I didn't give up."

The trip was just as harrowing as he expected. (In 1938, a National Geographic writer said it was the worst voyage in his 40 years of travelling.) The 100-meter ship rolled 20 degrees for most of the week-long journey, and on Day Four it keeled over by 45 degrees, toppling furniture and flooding the cabins.

"We almost flipped," Zamel says. "I thought I was going to die!"

Finally, one early morning, he saw the spectacular sight: a black mountain ringed with green rising out of the ocean. It was Tristan da Cunha. He was hoisted off the boat in a crate to a motorboat tossing in the waves below, which ferried Zamel and a research technician to the island.

The two researchers worked 10 hours a day collecting data on most of the 301 people on the island. They described the residents' genealogy. Everyone was descended from a handful of shipwrecked sailors and settlers who had come to the island in the previous century. There were only seven surnames on the island. Zamel also took down the islanders' history of respiratory and allergy symptoms, and the results of allergy tests.

Life was still simple, Zamel observed, but the islanders had been affected by their time in England. The women still spun wool from the local sheep and knitted incessantly: Zamel has a large collection of knitted sweaters and socks, a traditional departure gift. But now they bought wedding dresses from Cape Town. There was still no TV, but they imported videotapes to watch on VCRs. Lots of families had Land Rovers to drive to the potato patch five kilometres away. Potatoes were no longer the currency. They bought things with British pounds.

They still danced every Saturday night at the local community hall. In fact, they had a local band. Zamel brought drums, guitars and amplifiers for the band as a present to the island. The electricity was generated by a diesel engine.

After a month, the ship was due back. The day before his departure, Zamel took blood samples from nearly everyone on the island. The day began painfully: Zamel could feel he was about to pass a kidney stone, an experience he says is just as painful as having a baby. There was only one doctor on the island, and only a rudimentary hospital, but Zamel had brought plenty of morphine.

"I was happy," he says. "In fact, I was very, very high."

That night, Zamel hosted a party in the community centre and he danced all night. Two days later, he finally passed the kidney stone aboard the ship returning him to Cape Town.

When Zamel returned home, he got a call from a California biotech company, Sequana Therapeutics, of La Jolla. It was one of the new companies in the business of commercial gene hunting. Finding the genes for asthma, which could potentially provide a target for therapy, could be enormously lucrative. After all, 300 million people in the world have asthma, which is usually not fatal but a chronic disease. In other words, tens of millions of people might want to use a drug year in and year out to alleviate the symptoms. But it would cost a lot of money to find the genes.

Zamel had completed the first step: He had collected the genetic material from an inbred group of asthmatics. Now their DNA needed to be analyzed to pinpoint the genetic problem, which would require lots of fancy machinery and money to do it quickly. So the Toronto hospitals involved in Zamel's study made the deal to get Sequana to use its computer power to look for the distinctive patterns in the Tristanians' DNA. Then the California biotech firm obtained another $70-million from the German pharmaceutical firm Boehringer Ingelheim, to finance the hunt for the asthma gene that had begun with Zamel's trip to Tristan.

Then Zamel was criticized on two counts. First, the Rural Advancement Foundation International, a group that opposes patenting of crops, which has offices in Canada, complained Zamel was a genetic pirate, stealing valuable stuff from the Tristanians.

RAFI spread the word on the Internet that Zamel and his biotech partners were "committing acts of genetic biopiracy and in the process violating human rights of people from whom the data samples were taken."

Zamel counters that the Tristanians signed releases and were promised free asthma drugs if the research yields them. The German drug company paid for the modernization of the hospital to thank the islanders for Zamel's second trip there. The islanders also got about $50 each for participating, as recommended by the island council, in a deal reached while Zamel was there.

Zamel says he couldn't pay the islanders more: It would have broken the ethics rules written by the University of Toronto to prevent researchers from enticing subjects with large sums of money.

Sequana, which was sold and renamed Axys Pharmaceuticals, isolated a couple of genes after studying the Tristanians' DNA and filed patents for both of them, causing more concern among scientists about the privatization of human genes.

But Zamel is not concerned: "The information is in the public domain and can be used," he says. But no one can profit from it without being sued for patent infringement. "You can't use it to make a commercial profit," Zamel says. "I don't see a problem with it."

He shrugs off other complaints that this is one discovery that has slipped through Canadian hands. As a gene hunter, he found and collected the genetic material, but the California company analyzed it and the German pharmaceutical company is pursuing the tests on the target gene.

The German researchers have knocked out the gene in mice to see whether the loss makes them more or less likely to have asthma. Zamel is waiting to get some of the mice in Toronto, so he can study them, too.

He expects the gene sequence for the asthma gene -- which is one of several genes thought to be involved in the disease -- to be published in a prestigious scientific journal in the next year.

When it is published, his name will be on a long list of contributors. Zamel doesn't mind sharing the glory. "I don't care," he says. "Once I got my trip, who cares? I don't care about glory."

Zamel would much rather talk about life on Tristan. He has a huge stamp collection from the island and keeps a couple of thousand pounds in the local bank to finance his regular stamp purchases. The people there are in amazingly good health, he says, despite the fact that there is only one doctor on the island and no immediate care for drastic health problems. Yet the islanders' life expectancy is the same as the average North American's.

Maybe it's all the exercise and down-home living in a simple life fed by fish and potatoes and a close-knit community with no crime.

"It's a very neat society," Zamel says. Each male resident has three or four professions: fisherman, mechanic, farmer, butcher. Despite the welcome sign "to the loneliest island," Tristanians don't feel lonely, not when they're surrounded by family.

"The sense of community and organization is much better than a kibbutz," Zamel says. "It's a super-duper kibbutz."

© Copyright  2003 National Post

 

 

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