The University of Auckland has just wrapped up For All Our Futures - the biggest philanthropic campaign in New Zealand history - raising more than $380m directly toward new research. In the first of a two-part series, science reporter Jamie Morton looks at three critical questions some of these supported studies will ask about early life.
It's money in the bank, as far as Professor Wayne Cutfield is concerned.
"In terms of the potential benefits, you really can look at it like a return on an investment," he says.
"If you have a superannuation policy and put money in early, your investment will compound across your lifetime, but leave saving until much later, you won't get those same benefits."
Cutfield, a renowned paediatric endocrinologist based at University of Auckland's Liggins Institute, isn't talking about finance, but the importance of health in the first years of life.
It's an increasingly illuminating area of research, with studies drawing links between our wellbeing in later life, and the health of our parents before we're even conceived.
Scientists now understand that a mother's weight – and therefore diet and activity – just before conceiving a baby is almost as important as how much she gains during pregnancy.
The health of the father is similarly important, as obesity can regulate the way in which genes in sperm behave, raising risk in the child – a theory that wasn't demonstrated until 2015.
Cutfield's Liggins colleagues have zeroed in on this essential stage to find that premature birth can raise the risk of obesity, and that firstborns have greater difficulty absorbing sugars into the body.
More recently, the researchers have been investigating whether artificial sweeteners are just as bad for pregnant women as regular sugary drinks, and whether fish oil supplements taken in pregnancy can help combat weight problems in children.
"Planning around health and wellbeing prior to conception is a relatively new thing, but important, as a large proportion of pregnancies in New Zealand are actually unplanned," says Cutfield, who also directs a national science challenge focused on the area.
"For us, it's about understanding what an optimal environment and diet is for a mother, before and during pregnancy."
As it stands, researchers have built a crude picture of what this looks like and what mums should do: the obvious steps being stopping smoking and drinking, taking folic acid, boosting their nutrition and maintaining a healthy weight, and keeping any medical conditions under control.
"We can identify short-term risks. And if something happens around conception or during pregnancy, you can monitor and assess what that means during childhood," he says.
"The difficulty is having that longitudinal information that stretches well into adult life.
"Because, if a baby is born too early, too late, too small or too big – or if the mother is sick and vomiting a lot in pregnancy – all of these things have long-term implications for health and metabolism."
Can we prevent pre-term birth?
Each year in New Zealand, about one in 10 babies is born before 37 weeks gestation.
That's one premature baby born every 90 minutes, with more than 5000 babies having a difficult start in life each year.
Many sadly don't make it that far: spontaneous pre-term labour remains the biggest cause of death in babies.
Another big factor in pre-term labour is complications for mother or baby, such as growth problems in babies or pre-eclampsia in mums, with rates showing a 60-40 split between the two.
Several other trends stand out. Māori, Pasifika and Indian women are more likely to have pre-term births and when this occurs very early, their babies are less likely to survive.
Women and whānau are also not aware of the risk of pre-term birth, and measures they can take to try to avoid it.
Perhaps most troubling is that, despite growing insights, the rate of pre-term birth in New Zealand hasn't shifted in the past 10 years.
Dr Katie Groom, of the university's Faculty of Medical and Health Sciences, says research has already demonstrated measures that can prevent preterm birth, or at least improve survival when it happens.
Yet these steps – like using corticosteroids to improve newborn breathing problems, or delaying cord clamping for a minute – aren't being used consistently around New Zealand.
There aren't yet any national guidelines for clinicians on pre-term birth, and although there are some for managing pre-eclampsia and growth problems, they're not followed well enough.
These are gaps Groom and colleagues want to close with a new national project.
Having met various groups and built a general framework, they now plan to develop fresh national practice guidelines and form a network of specialised clinicians to care for most high-risk women.
The project will also strive to improve care for Māori, Pasifika and Indian, boost education and promotion of smoke-free services, and look further at the current midwifery-led continuity of care model.
"We think this work will lead to significant reductions in overall pre-term birth rates - and hence better outcomes for lifelong health of New Zealanders," she says.
"You should have the same chance of having a pre-term birth and having a good outcome after pre-term birth regardless of who you are, where you live or who cares for you in your pregnancy."
One Auckland mum who's been working with Groom sees the project as a legacy for the baby she lost five years ago.
Tina Allen-Mokaraka and Tasi Wilson's daughter, Carosika, was due to have been born on December 1, 2014; instead, Tina went into labour in the early hours of on August 9.
Rushed to Middlemore Hospital's delivery room, the couple were given a heartbreaking choice.
They could take Carosika straight to an incubator, where she'd have to remain until full term, with the likely consequence of severe brain damage; or let her pass.
"I couldn't even gather what was just said, because I didn't want to think," Tina says.
"To have that much time to decide your baby's outcome? It truly was the hardest decision I've ever made."
After discussion, she opted to let Carosika come; weighing just 700g, she died an hour after birth.
Last year, she read about a trial where the new clamping procedure was used on a 23-week-old baby, who survived to grow into a toddler.
She immediately sought out Groom to share her own story, and the pair met a week later at Auckland Hospital.
"Talking with her, was my first time I openly talked to anyone, about Carosika," she says.
"That chat we had, brought closure for me, as for four years, I carried so much guilt and thinking that I made the wrong decision, not giving my baby a chance - Katie reassured me, and I shared a moment of tears."
The couple have since agreed to discuss their experience, to raise awareness about preterm birth and the national project.
"It's been a long time coming, but we're so happy to finally have a legacy for Carosika."
Groom is also leading research into potential new therapies to promote growth – among them, using sildenafil citrate, used in the erectile dysfunction drug Viagra, to improve blood flow to the placenta.
The jury is still out on whether this intervention might help fetal growth restriction, with a small New Zealand and Australian trial having suggested some benefit, but one not seen as statistically significant.
Ultimately, she sees this trailblazing work as a continuation of that by medical researcher Sir Graham "Mont" Liggins, whose seminal 1972 findings showed how steroids gave premature babies a better chance to breathe and survive.
Can we find the roots of disease?
Another team has been looking at newborn health from a very different angle: using genetic information to help diagnose sick infants in intensive care.
As it's hard for doctors to make diagnoses in these cases, Liggins Institute molecular biologist Dr Justin O'Sullivan and colleagues are working out how they might be able to carry out whole genome sequences for the babies – essentially downloading their genetic make-up.
That would allow doctors to make a more accurate diagnosis, clearing the way for treatment.
It's just one example of groundbreaking work this group is doing in the DNA space that could help our children – another is research that has shed more light on the genetic drivers for type 1 diabetes, and on why seemingly unrelated diseases so often go together.
Their recent findings, published in two top scientific journals, reflect a deepening understanding that genetic sequencing is only the beginning of the story behind inherited traits and diseases.
And they highlight the potentially critical role played by genetic variants hidden among segments of our DNA once dismissed as "junk DNA".
"When we look about it is easy to see that our characteristics, including the chance of developing disease, run through families," O'Sullivan explains.
"Clearly our DNA has a role in this. We know that variation in the sequence of our DNA affects our chances of developing disease but we have struggled with understanding the bulk of these changes, because they occur in the non-coding – or junk - DNA."
Now that his team has worked out a way to identify what changes are happening – and which particular genes and biological processes they are affecting – we are a step closer to understanding how our DNA contributes to our chances of developing a complex disease.
"Right now, we're asking questions about why diseases with different changes in the non-coding DNA occur together?
"Just what do they have in common; what makes them unique; how the genetic changes interact with our environment; where does the development of the disease start in the body?
"It seems it is not always where we think. Answering these questions will contribute to a change in the way we approach the prevention and treatment of some complex diseases."
One project supported by the campaign, and led by Liggins PhD researcher Denis Nyaga, is focusing on Type 1 diabetes, a condition where the body's immune system mistakenly destroys the cells that make insulin in the pancreas, a large gland behind the stomach.
The result is that the body produces next to no insulin, meaning its cells can't uptake glucose from the blood and turn it into energy.
As a substitute, the body burns its fats, which leads to the build-up of dangerous chemicals in the blood, which is life-threatening if not treated.
People with the condition – estimated at 10,000-20,000 in New Zealand - depend on daily insulin injection to supplement the insulin the body cannot produce.
Though the exact cause is not yet known, scientists do know that if a child has a parent or sibling with type 1 diabetes, they are more likely to develop the disease.
Recently, genetic studies have identified genetic mutations that are linked to increased risk for the disease.
Nyaga's research aims at understanding how these genetic mutations could mistakenly be promoting the immune system to destroy the pancreas.
He has already completed a computational analysis of some of the genetic mutations associated with the development of type 1 diabetes, revealing those "new" genes important for increasing the risk of developing the disease.
Along with that, he has studied why polygenic risk scores for type 1 diabetes – used to predict the genetic probability of developing it – are so accurate.
In doing so, he and collaborators have pinpointed a particular gene, involved in regulating protein processing and signalling in the lung, which is likely key to that risk becoming actual disease.
Of course, it isn't the only condition we could better tackle by having a clearer picture of the intricate jigsaw puzzle that is our genome.
O'Sullivan says others range from asthma, Alzheimer's, Parkinson's and motor neurone disease, to depression, anxiety, ADHD and addiction.
"We are living longer – but a large part of our extended lifetime is negatively impacted by complex diseases that typically occur together," he says.
"If we can reduce the impact of these complex diseases, or delay their onset, this will have a significant impact on our quality of life."
Can digital innovation boost learning?
A third major programme is also looking to innovation to give Kiwi kids a better start – in this case, in the classroom.
Manaiakalani helps pupils in a group of Decile 1 primary and secondary schools to learn by working daily on digital devices, making full use of digital resources.
Not only can teachers share resources, parents can also click in to witness their child's work and progress.
Since launching in 2007, the number of schools in the programme has swelled to around 90 – and the impact on performance has been impressive.
After three years, a pupil at one of these schools will be on average, one year ahead of expectations.
"We've seen progress in writing at double the normal rate – and with reading and maths, one and a half times that," says Port England School principal Russell Burt, who works as a liaison between the schools.
Importantly, the initiative is school-led, and seeks to make school a more engaging and effective place for learners.
The focus on digital access seeks to redress inequity in access for learners, and harness the potential of all types of tools to make learning more effective.
Burt stresses that Manaiakalani isn't a tech programme, but one focused on pedagogy – or the theory and practice of learning.
"Many of the kids who come to these schools are starting from behind, educationally.
"Many have serious deficits that are slowing them down.
"Therefore it's necessary to try to accelerate their level of capability in reading, writing and maths, as they get toward those higher-stakes examinations in NCEA."
In using digital aids to boost pupils along, teachers and parents have had the help of researchers like Dr Rebecca Jesson, who have been observing and evaluating the interventions.
"We report back to the schools the patterns of achievement and progress for students over time, and we monitor results from classroom observations and questionnaires from teachers and leaders," Jesson says.
"We also match these against questionnaires for students and families, which the Manaiakalani Education Trust undertakes themselves."
They use the data to create what Jesson calls "sense-making" sessions with schools, to help them interpret the data and plan programmes accordingly, based on what students and teachers might most need support with.
"Education is not immune from the impact of the digital world. Schools are grappling with finding ways to harness positive effects of new technologies, while not losing sight of important fundamental principles," Jesson says.
"Our job is to tell them what's working, and challenge them to overcome what's not yet working as they would like."
Though encouraged by results so far, Burt says the "holy grail" would be having pupils in every class performing highly at all three subjects, simultaneously.
He remains in awe of the support the programme has received so far: by the end of this year, nearly $40m will have been raised.
"I had no clue that there were so many wonderful Kiwis who wanted to invest in things like this – and we are immensely grateful."
Campaign a success
The Campaign For All Our Futures - designed to fund research, innovation, and initiatives to support students - had the goal of $300 million when it launched in 2016.
But at a gala dinner on Thursday night, the university announced it had raised $380,271,165, at the time the effort wrapped up last month.
Chancellor Scott St John said the money raised was a crucial part of the university being able to continue to contribute locally and internationally.
"More than any other time, the world faces immense challenges. We are in the middle of a technological revolution, climate change, and an expanding and ageing population," St John said.
"Health and wellness issues are affecting the way and the length of time we live, while the needs of people must be balanced with the impact on the environment and the planet.
"By generating new knowledge and providing the highest levels of formal education, research-led universities have a unique role to play in meeting these challenges and creating a positive future for New Zealand and the world."
Also announced this week was the largest single donation ever made to the university.
Before his death in 2012, and inspired by the work of Distinguished Professor Sir Richard Faull and his team at the Centre for Brain Research, Hugh Green had helped set up the Hugh Green Biobank.
This is one of just a handful of institutions worldwide able to grow human brain cells.
As part of the campaign, the Hugh Green Foundation signed a gift agreement for $16.5m to fund the Hugh Green Biobank in perpetuity, and for a new Hugh Green Foundation Chair in Translational Neuroscience.
By the numbers
• $380,271,165: raised for the For All Our Futures campaign
• 23,592: separate donations made to the campaign, from more than 7000 donors
• $16.5m: the biggest donation, from the Hugh Green Foundation to fund a new bio-bank.
• $220: the very last donation received in the campaign, made by an Australia-based alumnus toward the Student Emergency and Wellbeing Fund.
• TOMORROW: How Kiwis can age better