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Daniel Sinnett is Director of Research at the Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-MontréalHandout

Let’s Talk Science and the Royal Society of Canada have partnered to provide Globe and Mail readers with relevant coverage about issues that affect us all – from education to the impact of leading-edge scientific discoveries.

Dr. Catalina Lopez-Correa is Chief Scientific Officer at Genome Canada

Diagnosing a rare disease is often a long and confusing journey for patients and families. About 25 per cent of patients wait five to 30 years for a diagnosis, up to 40 per cent are misdiagnosed, and some 50 per cent are never diagnosed at all.

Which of the 7,000 known rare diseases could it be? And then begins another journey: treatment. Genomics offers hope and solutions.

Genomics is the science of deciphering and understanding the entire genetic information of an organism, including us. That genetic information is called a genome and is made up of DNA and related molecules such as RNA and proteins. It’s basically a blueprint for how our bodies work.

It’s also a crucial part of precision medicine – disease prevention, diagnosis, treatment and prognosis that takes into account each patient’s variability in genes, environment and lifestyle.

No one understands the potential of precision medicine and genomics better than Laurent Tessier and his family. Laurent, 17, survived an aggressive cancer thanks to a genomics research program at Montreal’s CHU Sainte-Justine, launched in 2013 to provide children and youth with hard-to-treat cancers with personalized treatments.

More than a belly ache

Laurent Tessier (right) with mother, Hélène, and family pet, SushiHandout

Laurent was just nine-years-old when he began suffering from severe cramps that he chalked up to eating too much ice cream. But after his stomach began to balloon alarmingly, tests revealed liver cancer.

Over the next several years, Laurent endured a liver transplant and rounds of chemotherapy that caused so much pain that even morphine couldn’t touch it.

“When Laurent was recruited into our study, he was in palliative care,” recalls Dr. Daniel Sinnett, a molecular geneticist, and scientific director of the research program that oversaw his treatment. “He had only few weeks to live.”

Sinnett and his team got to work immediately. First, they sequenced Laurent’s genome, deciphering the order of the building blocks of his DNA. Those building blocks consist of four molecules called nucleotides. The nucleotides are adenine, cytosine, guanine and thymine and are represented by the letters A, C, G and T.

It used to take years and huge sums of money to sequence a genome, but with the help of high-throughput sequencing machines, the team was able to map out the letters’ order within 24 hours, and at a cost of about $1,500.

Next, they compared Laurent’s DNA sequence with other human sequences, looking for differences or mutations in the normal order of those letters that might have caused his cancer. As expected, they found a handful of such mutations.

Then came the hard part: picking out the guilty ones by comparing them to several databases of known cancer-causing mutations, and then further narrowing them down to those for which there exist treatments.

It was an anxious time for Sinnett and his team. “The clock was ticking,” he says. “He was at the end of his life and we really wanted to find something meaningful.”

After years of illness, a real Hallowe’en

The researchers were relieved to discover that while Laurent had a liver tumour, the genetic mutation responsible for setting in motion the biological chain reaction could be counteracted with a drug usually prescribed to children with brain cancer.

“So you’re not treating anymore according to a particular tumour, you’re treating according to a biological pathway,” says Sinnett. “At that time, no one else in the world had tried this treatment for this cancer.”

The brain cancer drug saved Laurent’s life. Within nine months, he was out at Hallowe’en trick or treating.

Since then, the CHU Sainte-Justine team has built on its success by recruiting other genomics research centres across the country into the pediatric oncogenomic precision medicine program for hard-to-treat children and youth.

In the past seven years, the program recruited hundreds of children with cancer who had exhausted all other treatment options. In 85 per cent of those cases, researchers have found promising actionable mutations, including those for which known treatments exist.

During this time, the researchers have also honed their ethical protocols, taking great care to get informed consent from patients and their families. “Families need to understand this is a research project. They’re planning for their child’s end of life and then we come to them and say we might have something, but it might not work,” says Sinnett.

Wider applications of precision medicine

Families also need to know that it’s possible genomics will uncover an inherited mutation that affects not only their sick child, but other members of their family.

It’s this last possibility that speaks to genomics’ wider potential. As Genome Canada’s Chief Scientific Officer, I know supporting the kind of research happening in Sinnett’s lab not only helps critically ill patients, but lays the foundation for precision medicine that benefits us all.

For example, we might find that some people have inherited mutations that make them ‘ultra rapid metabolizers’ of various drugs. This is important information for nursing mothers prescribed common painkillers.

Codeine is the active ingredient in some of these painkillers. An enzyme in the liver converts codeine to morphine, and a particular gene gives the instructions for making this enzyme. Some people have a genetic mutation that causes them to metabolize the codeine faster than others. Mothers with this mutation pass dangerous amounts of morphine through breast milk, which can harm their babies.

After genomics uncovered this mutation, Health Canada issued a warning regarding the use of codeine containing products for breast feeding mothers, saving untold young lives.

I’m happy to report that Laurent continues to thrive and the CHU Sainte-Justine team that made it possible takes great pleasure in that success.

As Sinnett says, “It was the first case where we had black and white success. That’s why Laurent is so important to the success of our precision medicine research program.”