The Murdoch Children's Research Institute Annual Showcase, held Tuesday 23 November, reflected on medical breakthroughs and health innovations that have come out of the institute in the last 35 years. Advances made in genomic testing over that period have changed how we can help critically ill children with rare diseases.

Advances in genomic testing technology: 35 years ago to now

Melbourne born Levi began having multiple seizures when he was just one day old. His EEG – brain wave tracing – was markedly abnormal and he needed breathing support.

Had Levi been born 35 years ago, doctors would not have been able to determine the cause of his seizures. Without this knowledge to guide treatment, Levi would have continued to have frequent seizures despite multiple antiseizure medications, and likely would have had very severe developmental impacts from these seizures.

35 years ago, genetic testing was in its infancy. To read the genetic code in our DNA - the blueprint for our body - scientists had to painstakingly separate individual bases and then, using photos, manually count them. This allowed them to only read a very small percentage of the DNA.

Associate Professor Sebastian Lunke is the Head of the Division of Genetics and Genomics at Victorian Clinical Genetics Services (VCGS) and MCRI.

“For people like me who have a passion for using technology to help sick children, this would have been incredibly frustrating,” he said.

Technology had improved substantially by the early nineties, with the first revolution in DNA sequecing. Automated Sanger sequencing meant that larger sections of DNA could now be read. But even with this technology it still took over a decade, hundreds of scientists, and over a billion dollars to sequence the first complete human genome.

For Levi however, this still wouldn’t have led to a diagnosis, as at that time there were only a handful of genes that were known to cause epilepsy, and none for the type of epilepsy he has. Even for those children that did receive a genetic diagnosis at the time, the journey often took many years.

But the technology has continued to advance.

The next revolution started in the early 2000s with the emergence of so-called next generation sequencers. These machines are standard of care today and can sequence dozens of complete human genomes in a short time, for only a few thousand dollars each. This has meant that today, thousands of disease-causing genes are known, and diagnosis is possible in months, not years.

But even this is not fast enough for critically ill children like Levi, who need answers in days.

Latest genomic testing evolution: Acute Care Genomics

Enter the Acute Care Genomics project, an Australian Genomics study co-led by Seb Lunke and Professor Zornitza Stark.

This project provides ultra-rapid genomic sequencing for rare disease diagnosis to critically ill children in intensive care across Australia.

“We have a strong focus on integrated, multi-disciplinary teams and translation of novel technologies into the clinic,” said Seb. “We always seek to improve how we use the technology, to find answers for ill children quickly and consistently.”

Through the Acute Care Genomics project, Levi received a genetic diagnosis in under five days. For his parents, this meant more than just an answer, it guided Levi’s seizure treatment, and he has been almost seizure free since he was three weeks old.

What do the next 35 years hold?

Dr Katherine Howell is a Clinician-Scientist Fellow and the Epilepsy Team Leader at MCRI, and a paediatric neurologist and epileptologist at The Royal Children's Hospital. Her work with severe, early-life epilepsies has informed changes to diagnostic pathways and clinical guidelines, benefitting patients, families, and health systems. Katherine is Levi’s epilepsy specialist.

“We’ve seen benefit from rapid genomic testing across many childhood conditions, not just epilepsy, but we don’t yet fully understand its potential” Katherine said.

Looking forward to the next 35 years of innovation and advancements, Katherine is excited.

“We are in the era of precision diagnosis, but we’re moving rapidly into an era of precision treatments, and hopefully cures. When treatments are available, rapid diagnosis will mean that we can implement them early when they will have the most benefit.”

You can watch Seb and Katherine’s interview and the full Annual Showcase.