MCRI: How vision to help children 40 years ago has left an incredible legacy
Philanthropist Dame Elisabeth Murdoch and pediatrician David Danks had a vision to “do something” to help children almost 40 years ago. This is their incredible legacy — and why it’s more important than ever.
Murdoch Children’s Research Institute (MCRI) is one of the top three children’s research institutes globally, renowned for its pioneering work in the science of stem cell and genomic medicine, public health and infectious diseases.
Despite the many accolades, its director Kathryn North says that MCRI’s mission is far from complete.
“We have made profound advances in diagnosis, treatment and technologies that have helped children live healthier, longer lives,” Professor North says.
“But we still don’t have the cure for many, and children born today are anticipated to have shorter life spans than their parents. The answer to these big issues is research, providing the evidence to underpin new approaches, new therapies and meaningful policy change.”
The health problems children face today are very different to when the institute opened in May 1986. Then there were few food allergies; obesity was rare and heart disease wasn’t on the radar as a future risk for children.
WATCH THE VIDEO WHERE DAME ELISABETH MURDOCH SHARES THE MOMENT THAT INSPIRED HER TO ACT
For the first time, North says evidence shows children are on a poorer health trajectory than their parents.
“One in three children are overweight or obese, increasing their lifetime risk of diabetes and cardiovascular disease,” she says.
“One in four children and young people are diagnosed with mental health issues such as depression and anxiety, and one in five are growing up in disadvantaged environments and already way behind their peers before they start school, and they don’t catch up.
“One in 10 children has serious food allergies and one in every 12 babies is born with a rare genetic disease; many of these leading to chronic disability. Around a quarter of children in hospital at any one time have one of these rare diseases.”
How to intervene and prevent this modern epidemic is the focus of the “brilliant minds” at work at Australia’s MCRI.
THE FOUNDERS
It has come a long way since the co-founders, philanthropist and child health advocate Dame Elisabeth Murdoch and pediatrician and genetics pioneer Professor David Danks, opened its doors almost 40 years ago.
They were a formidable pair driven to “do something” about the complex medical conditions affecting children with a determination to help them lead healthier, fuller lives.
Then the Murdoch Institute for Research Into Birth Defects, it was supported by the Murdoch family, the late Sir Jack Brockhoff, the Miller family, The Scobie and Claire Mackinnon Trust among others. In 2000 it merged with The Royal Children’s Hospital Research Institute to become MCRI.
Seeing children with terrible birth defects when she visited them in hospital had a profound impact on Dame Elisabeth, inspiring a lifelong commitment that would become her family’s legacy. Not just financially, although the extended family has contributed generously to MCRI, but also as global ambassadors pushing to attract the best to deliver the best.
LASTING LEGACY
Dame Elisabeth is the mother of Rupert Murdoch, founder of News Corp and publisher of this publication.
His daughter-in-law Sarah Murdoch, wife of Lachlan Murdoch, is co-chair and global ambassador of MCRI and founding chair of its Global Advisory Board. Granddaughter Penny Fowler is chair of The Royal Children’s Hospital Good Friday Appeal and her mother Janet Calvert-Jones, Dame Elisabeth’s daughter, was on MCRI’s board for 28 years and heavily involved in the annual Good Friday Appeal.
Sarah Murdoch says it has been a privilege over the last 25 years to watch MCRI transform into one of the top three children’s health research institutes globally.
“I remember the first time I toured MCRI, not long after Lachlan and I met, I walked the halls and I was overwhelmed with the enormity of the care: from the tiniest, sickest babies in neonatal to children isolated in wards fighting cancer to young people managing serious mental health issues,” she says.
“The moment it all clicked for me was when I walked just across the hall and met the researchers and scientists who were dedicating their lives to finding answers for these very same children.”
Sarah Murdoch says she also learned more about Dame Elisabeth and how and why MCRI came to be.
“When Dame Elisabeth wanted to build an advanced new hospital for children she wouldn’t take no for an answer from government, and when she saw the sickest children in their beds she wanted to get to the root cause of why they were so unwell, establishing a medical research institute to find those answers,” she says.
THE RESEARCH
North has led MCRI since 2013. A pediatrician and neurologist, she is building on the foundations of its three previous directors in professors David Danks, Bob Williamson and Terry Dwyer.
She says the founders could not have foreseen what would happen 40 years down the line, but they had set up the Institute to grow.
It now integrates laboratory, clinical, population and global health research groups under one roof with more than 1800 researchers working across over 150 common and rare childhood diseases and conditions.
“It is phenomenal,” North says. “Genomics is now underpinning so much of modern medicine.”
North says because of its reputation, MCRI also attracts brilliant minds.
“They are our greatest asset; this amazing group of scientists, researchers, clinicians, working together to solve the big problems in child health.”
INVESTING IN THE BEST
Italian-born Associate Professor Silvia Velasco is the inaugural recipient of the Sarah and Lachlan Murdoch Foundation Fellowship at MCRI.
The $5m perpetual fellowship was offered to attract the best researchers to help develop new treatments for sick children.
The stem cell scientist has trained at some of the most prestigious universities including MIT and Harvard in the US.
She was on track to continue her research in the US, but a chance meeting with MCRI’s chief scientist Professor Melissa Little saw her successfully apply for the inaugural fellowship and move to Australia.
The women knew each other by reputation and come from similar backgrounds: both are daughters of respected scientists and were encouraged by them to follow the “creative” side of science: research.
Velasco was highly sought due to inventing a robust method to generate models of the human brain using stem cells as a method to study brain disorders.
“I was a research scientist in one of the top institutes in the world. I had my green card. So this was very exciting for me because I was not looking for it,” Velasco says. “It was a big change in my life, not only as a scientist.”
She has now established her own laboratory at MCRI where she is using stem cell-derived 3D models of the developing human brain to study and identify new therapeutic approaches for brain disorders.
“I was lucky to also be able to join one of the top pediatric hospitals in the world (the Royal Children’s Hospital) and move my science more in the direction of making a difference for patients and families.”
Velasco says being able to connect with clinicians and researchers has shaped the direction of her science, as has the fellowship.
“Philanthropic funding really showed the trust that had been put into me and my research and what can be achieved.”
THE PIONEERS
A highlight of co-founder Professor David Danks’ career before he retired in 1995 was helping discover the genetic cause of Menkes syndrome. This disease affects the normal absorption of copper from an infant’s intestine, leading to brain damage, growth issues and death.
Dame Elisabeth had supported his early career development and encouraged Danks to further his studies abroad. When he returned he established the Genetics Research Unit at RCH, and later the Murdoch Institute for Research Into Birth Defects with Dame Elisabeth, which would become MCRI.
He is remembered as a “towering intellect” by Professor Bob Williamson, who succeeded him. Williamson, a geneticist, came from London to take up the role in 1995. A central figure in gene cloning, he was heading one of the first groups to isolate and “clone” a human gene and brought with him a broad vision of how genetics fitted into medicine.
“Every disease or trait: cancer, schizophrenia, how tall you are and how slim or fat, is determined by a combination of genetics and environment,” he says.
In his almost 10 years as director, Williamson helped move MCRI from being an excellent but (in world terms) tiny medical genetics group to an integrated, internationally respected child health institute with over 1000 staff.
“Success in integrating research with excellent clinical care, aiming for both prevention and cures, was in the DNA of MCRI, and we were one of the first to achieve this,” he says.
He passed the baton to leading population health expert Professor Terry Dwyer.
Dwyer remains at MCRI driving large studies including the International Childhood Cancer Cohort Consortium, which helped to explore environmental and genetic causes of childhood cancer. Under his direction, MCRI became its international co-ordinating centre.
He also strengthened MCRI’s global epidemiology credentials and its role in major cohort research.
Dwyer’s time at the helm positioned MCRI to bridge molecular science and population risk and saw it as much about preventing disease as discovering its mechanisms.
He now leads research which aims to identify children at risk of cardiovascular disease as adults, work, he says, that could save lives and health budgets in the future by reducing the incidence and death rate of heart disease in Australia.
“The new evidence we have comes from a study of 40,000 children measured for cardiovascular disease risk factors 40 years ago. We were able to follow them and find out which ones had heart attacks and strokes,” Dwyer says.
“This evidence has never been available before because it is a really big undertaking to do a 40-year-old study following up children; and it is really good data. What’s unique about our work is the impetus that the evidence gives to doing more in childhood.”
It is this world-first, life-changing research that MCRI is known for, and why it attracts the world’s best scientists and researchers.
ROYAL CONNECTIONS
In June Melissa Little was elected to the Royal Society in London; a fellowship of the world’s most eminent scientists.
To be nominated, a scientist must have delivered a breakthrough and/or produced a substantive body of research. Little did both.
She was recognised for her contribution to developmental and stem cell biology after creating a human kidney tissue model that could lead to new drugs for kidney disease.
“One in four people with renal failure will get a (kidney) transplant and the rest have a 60 per cent mortality rate on dialysis across a five-year period,” Little says. “It is an awful disease and it’s increasing in prevalence at six per cent a year globally.”
That’s because of the rise in cardiovascular disease, obesity and diabetes which is contributing to growing chronic morbidity.
“Recreating human kidney tissue is groundbreaking, it is a really big step up,” Little says. “We know we can replicate in the dish somebody’s renal disease. Now we are trying to modify it so it can be used as a tool for developing drugs for those diseases.”
It will allow for drugs to be tested on a human kidney model, rather than a patient or less accurate animal models.
“People think that kidney disease is something that happens to older people, but one in 15,000 children are born with a genetic form of kidney disease and many of them die,” Little says.
She came to MCRI a decade ago after 25 years with the Institute for Molecular Bioscience at the University of Queensland, attracted she says, to an institute that covered the breadth of medical research.
“From the really fundamental right through to how we can do a better job of delivering into community care,” Little says. “It is enriching to be in an environment that holistically looks at the challenges in health.”
She has since built a world-leading stem cell science program which is also supported by the global reNEW collaboration funded through the Novo Nordisk Foundation Centre for Stem Cell Medicine.
CHILDREN AT THE HEART
Professor Enzo Porrello is director of MCRI’s Stem Cell Medicine Theme, leads the reNEW collaboration in Melbourne and heads up a lab dedicated to finding cellular treatments for congenital heart disease.
His work is helping children like James Thornton, 16, who was born with half a heart.
James was given little hope of survival when he was diagnosed with a rare condition known as hypoplastic left heart syndrome. It is caused when a tiny switch doesn’t properly close.
It most likely happened in the early weeks of his development in utero, possibly even before his mum Nikki Burgess knew she was pregnant with her third child.
Porrello says: “By creating bioengineered heart tissues from stem cells, we hope to support heart function in children like James with congenital heart defects, prevent their hearts from failing and ultimately not need a heart transplant.”
HEALTH EQUITY
A sense of fairness in children’s health drives Sharon Goldfeld. A pediatrician, Professor Goldfeld moved into public health research because she saw some children were thriving more than others.
“I realised that even though I love being a pediatrician, I still am one, and it’s still important, (but) if I really wanted to make a difference, I had to work with populations of children,” Goldfeld says.
Now director of MCRI’s Population Health Theme, director of the Centre for Community Child Health at RCH and MCRI and deputy scientific director of Generation Victoria (GenV), she says policy is a big lever for change.
GenV began as a project to track a generation of Victorians, but the data will prove so important it is expanding into Generation Australia to help shape the future health of our nation and, ultimately, all nations.
It holds a treasure trove of information, brought to life by 120,000 Australians from nearly 50,000 families who provided samples – such as saliva, breastmilk, blood and DNA – to help researchers explore our health, how we live and how our environment affects us.
“It is an amazing asset that will really help to speed up research and fast-track it to policy,” Goldfeld says. “From a public health point of view, we’re working more on how we can build in the enablers for research.”
It is crucial, she says, to get data into the hands of frontline providers as a way of ensuring all children are equitably on track by the time they get to school.
“We’ve created the Australian Early Development Census, national data on children’s development on all children starting school, and we’ve changed the way that schools deliver oral language because getting oral language right means getting literacy right,” she says.
“Together we are really starting to reshape the way we talk about children and how we think about systems for children.”
Her vision today remains the same: “That every child starts school with an equal opportunity for life” and says that should be doable.
“I’m driven by inequities in children’s outcomes, the unfairness of it. By the time children start school about 20 per cent will be developmentally vulnerable. That is, they won’t be starting school on a level playing field. We have to find a way to change the systems.”
DRIVING IN MY CAR
It’s the simple things that bring joy to Professor Ravi Savarirayan. Like Sarah Cohen getting a car.
“She’s the first patient of mine who has started driving, and in a car without any modifications,” Savarirayan says.
“She doesn’t need pedal extensions and for a teenager that’s a huge quality of life thing. Sarah can drive a car like everyone else. She’s very happy about that.”
Sarah was born with achondroplasia, the most common form of dwarfism and caused by a genetic variation that affects around one in every 20,000 babies born in Australia.
Clinical geneticist Savarirayan is part of Victorian Clinical Genetic Services at MCRI and leader of MCRI’s skeletal therapies research group.
“About 10 years ago I heard about a precision treatment specifically for achondroplasia that had been successful in mice and I thought this could be a game-changing treatment for this condition,” he says.
He was right. And 72 children around the world, including Sarah, helped to prove his theory.
“The reason that I’ve come to somewhere like MCRI is that we see very sick children with rare conditions with significant health problems, some of which are life-limiting,” Savarirayan says.
“Children with achondroplasia have problems throughout their lives. Yes, diagnosis is important and management is important, but what has really driven me is to find better options and treatments for families.”
He came to MCRI because he wanted to manage and treat patients with genetic conditions.
“The trust that MCRI and the RCH have in the community is second to none and therefore families are willing to put their children through clinical trials to hopefully get to better treatments,” Savarirayan says.
“For the children in these trials not only are we decreasing the significant medical complications that they would have otherwise experienced, we are making an everyday impact on their quality of life.
“Through basic research, through to the translational research, and then clinical trials, we are in a position to offer lifesaving and health promoting treatments for those children.”
The treatment is a daily injection that “releases the handbrake” and allows average bone growth to resume.
It is now approved to treat achondroplasia in 60 countries including Australia, where Savarirayan was instrumental in making it available on the pharmaceutical benefits scheme to children from birth.
Making a difference, he says, is why he became a geneticist.
“We’ve shown that we’ve been able to decrease the medical complications rate in achondroplasia, including the incidence of sudden death in the first five years. That’s a huge outcome,” Savarirayan says.
“At a place like MCRI where we go from the basic science to implementation to children, and then evaluation, it’s kind of a unique environment to be able to do that kind of work.”
The trial, he says, had also exceeded his expectations.
“We’ve shown the medication is safe in children and we’ve been able to show that the growth rate in children treated with this medication approximates that of children without achondroplasia,” Savarirayan says.
“It takes the pressure off the spinal cord and the brain, and allows children to be taller and more proportionate and more functional, with a better quality of life.”
He is now testing an oral formulation that he hopes will be available for families in the next year.
“It will be something you just sprinkle into your WeetBix. So we’ve really come a long way.”
THE FUTURE
Sarah Murdoch says MCRI had not historically enjoyed the level of funding that, for example US institutes receive.
“Despite this, MCRI is still in the global top three for research impact – showing what a great investment MCRI is,” she says.
“Philanthropy is critical and I have seen first-hand the difference it makes, particularly in seeding research. We want to continue to attract the brightest minds in research in order to create lasting, multigenerational impact, and we also hope to inspire others who have the capacity to donate to ensure MCRI – and thereby all children and adolescents – can thrive in the long-term.”
She was inspired by Dame Elisabeth, who she says was always smiling and had an open heart for all.
“I think of her always and I am honoured to be a part of this remarkable place as we work to continue her legacy.”
It is a legacy that may also see fewer children need to come into hospital.
Professor North says that is the vision. “And if they do, they’ll stay a much shorter time because they get the right treatment the first time.”
Sarah Murdoch says Dame Elisabeth would be incredibly proud if she could see MCRI now.
“It is truly breathtaking to contemplate the breadth and depth of the work of the institute, its impact on medical advances globally, and the potential it has to change the lives of children for generations to come,” she says. ■
Murdoch Children’s Research Institute celebrates its 40th anniversary in May.
Originally published as MCRI: How vision to help children 40 years ago has left an incredible legacy
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