Scientist who searches for one-in-three-billion mistakes

Fancy looking for a single spelling mistake in 1,000 hand-typed copies of War and Peace?

If so, you are likely to get on well with Kathryn North, the redoubtable, razor-sharp yet decidedly congenial director of Melbourne’s Murdoch Children’s Research Institute (MCRI), Australia’s largest organisation investigating childhood illness. North has made it her life’s mission to delve deep into the three billion bases that make up the human genome as she hunts for the errors that cause disease.

The 57-year-old greets me at her home in a leafy inner suburb of Melbourne. Her black dress and dark-rimmed specs is all-purpose corporate kit for someone wielding a $100 million-plus research budget and whose job includes meetings with the likes of the institute’s founding patron Rupert Murdoch and spouse Jerry Hall. (For the record, Hall “was really warm” and  “just relaxed everybody”.)

But North has a softness of tone and benevolent air that speaks to her past as a paediatrician in Sydney in the 1990s, where she specialised in neuromuscular disorders. However, the lure of the children’s clinic would face stiff competition from her profound love for research.

She honed her early skills as a geneticist at the University of Sydney where, in 1994, she earned a doctorate in neurogenetics. Barely taking a breath, she was off to Harvard University for a postdoctoral fellowship under Louis Kunkel, famous for discovering the gene for dystrophin and the mutation that causes Duchenne’s muscular dystrophy.

North returned to Sydney in 1995 with a grant to launch her own lab at the newly minted Westmead Hospital. During this time, a plum position opened up as a paediatric neurologist. But North’s career card was already signed to research. “Everyone said: ‘Your job’s come up, Kathy,’ and I didn’t even apply for it.”

Her own reputation took off with her 1999 discovery of the ‘gene for speed’ – a variant of the ACTN3 gene that codes for a protein producing the explosive fast twitch muscles of elite sprinters. Her CV now bristles with achievements, including nearly 300 journal articles, assorted professorships and a membership of the Order of Australia.

But there have been hurdles, one deeply personal. In a freakish fall from a swing aged three, one of her eyes was irreparably gouged by a piece of metal, leaving her disfigured and  subject to endless playground taunts.

Buoyed by her mother, the experience was ultimately galvanising. “I’d come home and be a bit upset about it,” North recalls. “Mum just said: ‘What is there that the other kids can do that you can’t do? Just show them.’”

North clearly took the advice.

Her work includes heading up Australian Genomics, a collaboration of 70 Australian institutions whose mission is to bring precision medicine – knowledge of how an individual’s’ genes influence their health – into standard medical practice.

She was one of the experts behind The Future of Precision Medicine in Australia report, commissioned by the federal government and published in January. At the report’s launch in Melbourne, she introduced Louis Clarke, a four-year-old boy diagnosed at five months with a rare genetic disease. Doctors did not expect him to live for more than a few years.

But in 2014 he participated in a research study that sequenced his genome. “Very quickly we were able to identify that he had a change in a gene, a disorder that affects 1 in 10 million, affecting the transport of thiamine and biotin in the brain,” North says.

Immediate treatment with high doses of those two vitamins, which play key roles in cell metabolism, could not reverse Louis’ brain impairment but did stop further deterioration. His death sentence has been removed and his parents Martin and Amy still have their little boy, North says with clinician’s pride.

She is something of a crusader for the genomics cause, and both efficacy and economics appear to be stacking up behind her. A recent study of “difficult to diagnose” children, led by Zornitza Stark at the MCRI, found that traditional testing, which often includes painful tissue biopsies, unearthed diagnoses in 11% of cases at an average cost of more than $27,000. Gene sequencing, by contrast, snared the problem in 55% at a little more than $6,000 a pop.

The tests are getting faster, too. “We’ve just finished a pilot,” North says, “where we can use genomics in the intensive care setting, and we can do the sequencing acutely.” The study reduced the time from blood pull to sequencing to just 65 hours.

Aspects of precision medicine are particularly data hungry. Researchers are using machine learning to trawl vast, pooled genetic databases to link tiny errors in DNA with disease, a humanity-wide project that promises to greatly refine diagnosis.

So should we all be sequenced at birth, a la Gattaca? “If we started now and just did blanket sequencing, there is a big question mark over the benefits to the individual,” North says.

One problem is that sequencing every newborn could yield a Pandora’s box of genetic variations whose health implications are unclear, a potential nightmare for counsellors tasked with explaining it all to parents.

When it comes to the issue of storing all that data, there is also the problem of public concern due to a lack of understanding about how DNA information is kept. “People who haven’t been fully informed watch CSI and think their DNA could be planted at a crime scene,” North says.

Improving awareness of genomic medicine is therefore one of her goals. She relates the experience of patients at Melbourne hospitals invited to have genome sequencing. When well informed and reassured of their privacy, she says, 98% have agreed to share their data for use in research.

It is hard to say how much North’s schoolyard trials have shaped her. What is clear is that her relentless approach to discovery springs from a serious appreciation for inclusion.

“I love networks,” she says. “Bringing people around a table and getting them to be greater than the sum of their parts.”