Professor Jozef Gecz, a human genetics expert at the University of Adelaide, has made significant strides in understanding how DNA variations shape brain conditions such as intellectual disability, autism, epilepsy, and cerebral palsy. His research combines large-scale genetic analysis with insights that have pinpointed specific DNA changes behind these disorders, leading to major breakthroughs in understanding their origins.
From Moon to Rocket: The Human Genome
Professor Gecz compares the journey to reaching the moon. 'We see the moon every day... but we needed the rocket,' he says. 'For me, the rocket was really the completion of the human genome reference DNA sequence. That’s where we could finally delve deeper into the understanding of our biology, of our suffering.'
Rather than studying normal brain function, Professor Gecz examines what goes wrong during development. 'You better understand how things work when they break,' he explains. 'I started to study disability, and through that, to understand how we are supposed to work by these examples of the natural experiments there – or experiments of nature where things didn’t go to plan.'
Complexity of Genetic Discoveries
Early estimates suggested there might be 100,000 genes; now scientists know there are closer to 20,000. Yet despite the reduction in numbers, complexity has grown. 'We totally underestimated the complexity,' he says. 'Now we have about 5000 genes where something goes wrong and leads to a clinical outcome – and the majority of these are affecting neurodevelopment, like the brain.'
For many years, people thought cerebral palsy was a consequence of bad birth. 'Now we know that up to one third of these children ... it’s driven by major genetic causes. The causes are there from the very first days of life – from conception,' he adds.
Genes and Environment: No One-Size-Fits-All
Such findings highlight the intricate connection of genes and environment. 'One alteration doesn’t always cause one outcome,' Professor Gecz says. 'One alteration can cause multiple different outcomes – even identical twins can present differently. People say, “That’s not genetic, because identical twins are identical”, but that understanding has completely changed.'
Barriers to Genetic Testing
Despite breakthroughs, genomic testing remains out of reach for many. The tests can be expensive, Medicare only covers certain conditions, and proving eligibility can be difficult. 'The one thing we don’t have ... is that people have access to these tests,' he explains. 'Medicare only covers certain conditions, and if you don’t fit that box, you need to pay thousands of dollars. So my goal is to make these tests affordable and widely available ... sooner or later, each one of us will require a genetic test to live a better and healthier life.'
Developing Treatments Through Genetics
Beyond diagnosis, Professor Gecz is developing treatments – working out the best ways and timing to tweak DNA so individuals can be empowered by understanding their own genetics. 'We all just want people to have a healthy family,' he says. 'Our goal is to make sure everyone can benefit from this knowledge so people can live healthier, fuller lives without the uncertainty that comes from not knowing what their DNA looks like.'
Personal Journey into Genetics
Professor Gecz’s path was shaped by adversity. 'I was always fascinated by adventure, looked for puzzles and was challenged by the unknown. Mathematics and physics were my favourite subjects in early days. Medicine was beyond my reach under the Slovak communist regime and rules (due to my family background as my mum was a daughter of what was considered a rich farmer and father was French born) so I had to find a way to work with and help people differently.'
At university, he chose a double degree in general biology and anthropology, eventually landing on human molecular genetics. 'I naturally gravitated to genetics of human traits as a means to understand how our organs and brain in particular work.'
Around 1986, only a handful of human disease genes were known, and he worked on those for early prenatal diagnosis, prognosis, and prevention. Over 40 years, he contributed about 350 disease gene discoveries to the total tally of about 5000 human disease genes, leading the field in intellectual disabilities, epilepsies, and most recently cerebral palsies.
He focused on 'naturally occurring variation' – human subjects with genetic conditions affecting brain function. This was not a generally accepted strategy, as biologists used animals and cell models, while doctors looked after patients. He was keen to make humans and their cells the best model to study diverse brain conditions.
'Almost all our traits, including behaviours, movement, or physical performance have some genetic influence. Equity of access to genetic testing is hugely important to me as well as appreciation of the fact that many conditions, often considered to be due to e.g., injury or medical malpractice, like cerebral palsy, may and do have significant genetic contribution. That is why a genetic test should be available to everyone and at an affordable price. Understanding of our genetics can and does make a difference for our current and future health.'
