Origin stories: the Liggins Institute at 25

Distinguished Professor Dame Jane Harding’s unassuming office at the University of Auckland’s Liggins Institute bears little evidence that she is one of the world’s foremost experts on pregnant mums and their babies.

Her groundbreaking work has significantly reduced the risks of brain damage for newborn babies with low blood sugar levels. It has also proved the safety and effectiveness of steroid injections given to mums to boost their babies’ lungs before birth – a treatment that has saved hundreds of thousands of preterm babies worldwide from death or disability.

Tucked away on a shelf in her office, however, is a framed photo that provides a clue to the origins of this internationally significant work. Taken 25 years ago, it features Dame Jane standing between two other giants of New Zealand science: fellow clinical professor Sir Peter Gluckman, who became the Liggins Institute’s first director, and Sir Graham Collingwood (Mont) Liggins, who made history with his discoveries about how to treat premature babies, and after whom the institute is named.

These three researchers provided a critical foundation for the world-leading work of the institute today. 

Big research in a small country

Dame Jane once described the founding of the Liggins Institute as a “bold experiment” to foster big, globally significant research from a small country.

And the experiment worked. The institute brought together internationally recognised scientists from a wide range of disciplines with a singular aim: to research the links between early-life events and later health risks, and to use that research to improve outcomes for babies and children.

It’s a focus exemplified by the breakthrough 2013 ‘sugar babies’ research, carried out by Dame Jane and colleagues, which showed through a clinical trial that rubbing a blob of an inexpensive sugar gel inside the cheek of babies with low blood sugar in the first 48 hours after birth rapidly improved their sugar levels, thus reducing their risk of brain damage. The treatment, which is now first-line care around the world, also reduced the need for these babies to be admitted to neonatal intensive care units.

The institute’s ‘big research’ saves lives – and reduces healthcare costs.
A quarter of a century after its inception, the Liggins Institute has more than 150 staff, including 35 PhD students, six professors and two associate professors. It publishes close to 150 papers a year in peer-reviewed journals and has 214 living postgraduate research alumni, many working as clinicians in hospitals across New Zealand and abroad.

“One thing we all have in common as humans is that we were born,” says professor of genomics Justin O’Sullivan, who has been the Liggins Institute director since 2023. “So, at the Liggins Institute, we focus on that event: the impacts of things that modify birth and that make the outcomes of birth better.

“The challenges that relate to that event change all the time and they’re not easy to solve. And that’s the beauty of it: the challenges are constant.”

One example, he says, is the institute’s newborn genomics programme, which uses DNA sequencing to identify rare disorders in very sick newborns.

“We sequence the baby and their mum and dad, and then we identify the genetic changes that are contributing to a baby being in intensive care,” explains Justin.
“The goal is to help clinicians quickly identify the condition that the child has, and how to treat or otherwise care for that child.”

Since Liggins bought two genomic sequencing machines in 2023, it has been able to map the DNA of more than 60 newborns and their parents.

In a project that started in March, Justin and his team are now working alongside doctors at Starship Children’s Hospital to fast track development of new treatments for individual children with rare diseases after they have been diagnosed using the genetic sequencing technology. The team has received a $5 million anonymous philanthropic donation to carry out the work over five years.

“Through our clinical trials, our newborn genomics projects, our ongoing work on the best way to feed preterm babies [see ‘Food for life’, below], research around AI in healthcare, and all our other research, the Liggins Institute has made massive contributions to human health,” says Justin.

“There is so much that we are doing now – and that is still to be done.”  

What makes us what we are?

The hypothesis that events or conditions in a person’s early development could influence their risk of disease in adult life is known as the Developmental Origins of Health and Disease or DOHaD. Developed by English physician and epidemiologist Professor David Barker in the 1980s and ’90s, DOHaD made connections between low birth weight, for example, and coronary artery disease, hypertension, obesity and insulin resistance in adults.

Sir Peter Gluckman once said the Liggins Institute was founded to ask perhaps the most important question in medicine: What makes us what we are? The institute’s research, he noted, “will determine how the next generation grows to be healthy and more resilient both biologically, intellectually and even in social terms”.

When it came to naming the institute, Sir Peter approached Mont Liggins, famed for his pioneering work in the late ’60s and ’70s into the birth process and the discovery that giving steroids to women at risk of preterm birth accelerated fetal lung development – and often saved their babies’ lives.

“Mont represented the kind of research I felt the institute should have,” said Sir Peter. “Namely high-quality basic science that had the capacity to be translated to make a difference.”

Dame Jane later undertook studies involving the first cohort of babies whose mothers had received the antenatal corticosteroid injections. She and her team looked at the long-term effects of the steroids on the health of the now-adult babies 20, 30 and 50 years down the track.

The research consistently demonstrated the steroids were safe, and the published papers provided the reassurance doctors around the world needed.

“One of the reasons steroids were not taken up as quickly as they should have was people were worried there might be adverse effects in the long term,” says Dame Jane. “We were able to use that data to answer those questions.”

Clinician researchers

Professor of paediatric endocrinology Wayne Cutfield joined the Liggins Institute in its early days, attracted by the opportunity as a paediatrician and academic to focus on research with potential to change outcomes for patients, and to collaborate with researchers across disciplines.

“It created collaborations that would otherwise never have happened,” says Wayne, who served as the institute’s director from 2009 to 2015. “We can achieve so much more by bringing disciplines together than if they worked separately.”

Wayne points to the institute’s research into the gut microbiome, which has included looking at the role gut bugs play in the development and treatment of conditions including a gut-infecting bacterium called Clostridium difficile, obesity, autism, anxiety and anorexia nervosa. His interest in the area was first piqued more than a dozen years ago, leading to an initial study, working with Justin, looking at the development of the microbiome in children born prematurely.

“Justin and I hadn’t worked side by side before, but we got on like a house on fire. We were like the odd couple – a paediatric endocrinologist and a molecular microbiologist. You couldn’t think of two fields further apart – but we’ve become a very effective and powerful team because we’ve got this balance of basic science and clinical insight.”  

Gut bugs have become a major area of research for the institute, leading to internationally significant findings.

One groundbreaking study, carried out nine years ago, involved 87 obese adolescents receiving a faecal transfer (taking ‘good’ gut bacteria from healthy donors and giving them, in capsule form, to people with a less healthy microbiome) to see if it would make a difference to their health and weight.

A follow-up study, the results of which were published last year, found the original overweight teens who received that single transfer had a reduced risk for a range of metabolic changes that can lead to heart disease, stroke and diabetes, compared with participants who received a placebo.

The hunt is now on to identify which bacteria among thousands are most effective for the treatment of specific conditions, including metabolic syndrome and anxiety. The aim is to then scale up production of those ‘good’ bacteria to create super probiotics as treatments.

Wayne is now leading the OAK Study, which is treating toddlers prescribed antibiotics with a type of complex sugars found in human breast milk. Antibiotics have a negative effect on the fragile early gut ecosystem, and the study aims to see if these sugars protect toddlers’ developing gut microbiomes and prevent them from later developing obesity, asthma and eczema.

Like many of the institute’s researchers, Wayne is a practising clinician. He says clinical connectedness has helped recruit a range of experts to work on the microbiome research, and it also gives him crucial insights into the issues faced by patients.

Dr Ben Albert, a consultant paediatrician at Starship and a Liggins Institute senior research fellow, is another whose work in the field influences his research and vice versa.

Currently he’s researching the role a father’s obesity plays in the health outcomes of his children, given recent international research showing how a father’s lifestyle can significantly alter epigenetic markers in his sperm.

He says practising as a doctor allows him to help people directly, while being a researcher allows him to work on longer-term projects that have potential to more widely impact clinical practice.

“Liggins champions the idea that early-life factors matter in adulthood, so if we can find effective treatments in early life, they could ultimately prove really cost effective and important,” says Ben.

“We have a narrow window of opportunity, but it has such potential to improve the health of our society overall.”