There’s something fishy about how prenatal Omega 3 fatty acid research went from hypothesis to implementation in just five years. It’s not about money. It’s not about ethics. It’s not about what you know. But it is about who you know.
“They say it takes a village to raise a child,” says internationally acclaimed clinical nutritionist Professor Maria Makrides. “You could say the same for research.”
Professor Makrides was appointed executive director of the South Australian Health and Medical Research Institute (SAHMRI) in August.
Ten years ago, SAHMRI was an idea for a development on an empty block alongside an eye-sore railway on the edge of the central business district in what was then, fairly sleepy Adelaide, the capital of South Australia (SA).
As it celebrates its tenth anniversary this month, it’s a vibrant, world class bio medical hub, hosting thousands of staff across multiple universities and agencies, and making global health breakthroughs.
Makrides is happy to share the secret of this success.
“It’s about connections,” the 2022 South Australian Scientist of the Year told Cosmos. “And when you make the most of those connections, you end up with great outcomes.”
Connections – and a healthy dose of serendipity – is how the Adelaide BioMed City precinct came to exist, says former SA health minister, John Hill.
Out-of-date facilities, fragmented research groups and a falling share in federal research funding in the early 2000’s prompted a delegation of SA academics to approach Hill shortly after he took up the job in 2005 under the then Mike Rann Labor government.
“I remember walking around and seeing people working in corridors and broom closets, and God knows what else, all scattered all over the place.”
“I went to talk to the premier about the state’s medical research woes, I found it very hard to explain my rant. What was it we actually needed? I didn’t really understand it myself.”
But Hill had met Adelaide stockbroker Alan Young, who’d been raising serious money for the Flinders Medical Centre, in Adelaides’s southern suburbs. “He had some great ideas. So I mentioned him to the then CEO of Health Dr Tony Sherbon. And he suggested Professor John Shine from the Garvan Institute in Sydney could help flesh them out. So together they produced the Shine Young Report laying out a plan to produce a focal point linking all the universities and individual research groups together.”
That focal point would become what’s now known as “The Cheesegrater,” a ten-story building to house a new biomedical precinct. But the state government didn’t have the necessary $200 million in hand.
And then the Global Financial Crisis hit.
“The Rudd Federal Government was suddenly calling out for shovel ready projects to keep the economy moving,” he told Cosmos. “This was shovel ready.”
Makrides says she had experienced the trials and tribulations of standalone, isolated medical research into Omega-3 before SAHMRI’s distinctive “Cheesegrater” office opened on Adelaide’s North Terrace ten years ago.
“It’s an idea that blossomed,” Makrides says. “To begin with, there was the SAHMRI building – and a paddock! Then the new Royal Adelaide Hospital was built next door. Now we’ve got two universities, and the Australian Bragg Centre with its proton therapy unit is under construction.”
Makrides talks about connections. “This is where my SAHMRI story started. We asked if we gave mothers extra Omega-3 during pregnancy, would that result in better outcomes for the baby?”
SAHMRI – then still a cheesegrater in a paddock – facilitated the rapid formation of a new study involving 2500 pregnant women.
The answer turned out to be “no.” Once a baby has healthy levels of Omega-3, their development follows an established path.
But, buried among the details of their research notes was something intriguing. Mothers given supplements appeared to carry their babies closer to full term.
And that answered a pressing question the researchers hadn’t asked.
The data suggested no difference in health issues. And the longer gestation periods were enticing.
“Finding such a secondary outcome could have been a furphy,” Makrides says. “But it could be a critical outcome if real. So we thought, as a team, ‘hey, you know, we actually should do another study.’”
While 2,500 volunteer mothers were needed to generate viable results for the original Omega-3 preterm study, a whopping 5,500 were needed to validate the gestation extension question.
But by now, the SAHMRI in the “cheesegrater” was no longer alone as the evolution of North Terrace into the Adelaide BioMed City precinct was advancing.
New connections had been made.
“People know people,” says Makrides. “And SAHMRI is built on a partnership model. We have exposure to people that you otherwise wouldn’t have.”
Building just such a collaborative network was a part of getting the precinct rolling, says Hill.
“Premier Mike Rann and I went about convincing the universities that they should get involved. That was an interesting process. They were a little bit nervous about sharing their knowledge, staff and resources.”
The researchers themselves, however, were enthusiastic.
“One of the powerful things about researchers is that the institutional arrangements they work under really don’t matter to them so much,” says Hill. “It’s about what they’re trying to do, and who’s the best person for them to cooperate with to do that.”
In the end, the government was able to “massage things” to guarantee every project was a joint process through SAHMRI with research papers and grant money credited back to the universities and institutions. “There was some hesitation. I think they weren’t sure what they were getting themselves into. But eventually everybody signed off.”
Makrides’ team was quickly able to reach the 5,500-volunteer target needed. About 2,000 of those were recruited in South Australia alone.
“If I didn’t know some of the people at the Lyell McEwin hospital, then my colleagues at the Women’s and Children’s Hospital or Flinders Medical Center would know their colleagues at that location and put us in touch,” she explains.
“We were able to put researchers there so as not to be a cost or hindrance to the health services. But the midwifery staff in the antenatal clinics were essential partners in making sure mothers had the confidence to engage with our staff.”
The results were clear. Only women with low Omega-3 fatty acid levels recorded a reduction in premature births when given supplements. Those with already adequate levels demonstrated no benefit.
“This is the usual story in nutrition,” says Makrides. “The importance of this study compared to the earlier one was that we measured Omega-3 status, and this was the key to helping to understand what was really happening.”
“We developed a blood spot technology to measure fatty acids from a simple finger pinprick,” Makrides recalls.
This produced the evidence needed to prove supplements could reduce the risk of preterm birth among depleted mothers by more than 70%. So, how quickly could such a test be rolled out in the health system?
“We talked to our friends at SA Pathology, and they said: ‘Maria, that’s all very nice. But all of our workflows and systems rely on blood serum.’”
Just as engineers are the pragmatic side of architecture, so are pathologists and health practitioners to medical research. And early exposure to their real-world environment speeds up the research implementation process.
Australia already has a well-established set of standard blood tests for pregnant women. And SA Pathology advised that the Omega-3 test would have the best chance of being broadly adopted if bundled among those as an optional extra.
“So we had to go back to the lab,” Makrides explains.
Were the whole blood signals also found in serum? How did the cut-off points translate? Could this be validated?
“Fortunately, we had a lot of samples from these same women in the freezer. So we could work out the equation of matching the Omega-3 value in whole blood against the serum level,” Australia’s pregnancy care guidelines were updated in 2021 to provide evidence-based recommendations for supplementation for women who are low in Omega-3.
“We still have a way to go,” says Makrides. “But the average for that sort of translation is about 17 years. We’re very happy with our turnaround time.”
Getting a flagship building to anchor a new health precinct was also something of a challenge, says Hill. The inevitable budget questions kept being asked: Why not half the size? Why not a cheaper building? Why the expensive radiation beam cyclotron in its basement?
“It was really through Alan Young and Chairman Raymond Spencer’s persistence and vigilance that we got the architectural model that we got – something that would inspire young people towards science instead of walking past just another glass box. And the cyclotron had some very necessary direct health benefits, as well as research benefits”.
“There are international commercial companies already looking at Omega-3 test and treat programs,” says Makrides. “They’ve sought our advice and programs are now available in the US, Netherlands and Belgium. And that’s a result of one of those public good aspects to this particular research – it doesn’t have a patent around it.”
Makrides says success was a result of being able to balance focused research with pragmatic practitioner input.
“We want to move quickly. We want agility. We want to be able to deliver things. And to do so, we must stay focused on the core business. And that’s what industry likes to see. They don’t want to get trapped in paperwork or tied up with bureaucracy.
“But for that to happen, you need connections. And for that, the building of trust is vital. That’s essential for all our partnerships.”