Margaret Brimble is a synthetic chemist, or a “molecular gourmet chef”, as she sometimes describes herself. The distinguished professor and her team – spread across two labs at the University of Auckland – design and make molecules with therapeutic properties, using a process that can take several years and doesn’t always end in success.
Her job demands not just creativity, but a remarkable amount of patience and persistence. “It can be incredibly frustrating,” she admits. “Part of this job is being prepared to not get instant success … you’re in there for the long haul, not instant rewards.” A few welcome rewards have come recently. On November 21, Brimble was awarded the Rutherford Medal, New Zealand’s top science award, at the Royal Society Research Honours Dinner at Auckland War Memorial Museum. Strikingly, of the 14 major prizes awarded in the sciences and humanities, three went to Brimble.
As well as being only the second woman to win the Rutherford Prize, Brimble walked away with the Hector Medal, which this year goes to the country’s top chemist, and the MacDiarmid Medal, which recognises scientific research with human benefit. Other scientists have been known to win three medals in their lifetime, but no one has ever won three in a year. The achievement mentioned in the citation for each of these medals is a drug candidate designed to treat traumatic brain injury, or TBI. Up to 90 New Zealanders are affected by TBI each day, mostly from falls and motor vehicle accidents, but there are no drugs
to treat it.
In the United States, where shootings are a factor, TBI is the primary cause of disability and death in people under 45. Much of the damage from TBI occurs after the initial injury, from bleeding, swelling and convulsions. The drug candidate designed and synthesised by Brimble’s team – known as NNZ-2566 – has so far proved effective in reducing inflammation and injury-induced seizures.
“Normally it’s big pharmaceutical companies with huge teams that do this sort of work,” says Brimble, “so it’s a great feat for a small academic group to get this far.” NNZ-2566 was developed by Neuren Pharmaceuticals with US$18 million of funding from the United States Army, and is now in phase 2b human clinical trials.
TOO SQUEAMISH FOR MEDICINE
Brimble has been keen on science since childhood. As a top student at Diocesan School – she was joint dux in 1976 – she was expected to pursue a career in medicine. “But I couldn’t deal with the blood and guts and tissue,” she says. “I hated the biology labs and had to leave the room when they were dissecting rats, or sheep’s eyes. I just couldn’t do it.”
Chemistry, though, she loved. Not only could she do the experiments without gagging, but she was attracted by the black and white nature of the subject. “I really struggled with very arty subjects where we had to write essays, but with chemistry, maths and physics there was always an absolute logic and only one way to do things. It was very clear and focused and I liked that; I liked the logic.”
She won a scholarship to study Latin at Victoria University but instead chose maths and chemistry – which is where she found her niche. She completed an MSc in chemistry at the University of Auckland, then won a Commonwealth Scholarship to do a PhD in organic chemistry at the University of Southampton in England. “What really turned me on to organic chemistry was the power and creativity of making new molecules. You go into a lab and draw a structure of a chemical and then you make that compound … you can confirm it by using spectroscopic techniques so you know exactly what you’ve done.” So, although she didn’t pursue a career in medicine, she ended up in the related field of medicinal chemistry, “where you’re trying to come up with new therapies, new drugs to treat disease”.
IMPROVING ON NATURE
Brimble’s work on TBI drugs is only one highlight of a very accomplished career. In her first lab, in the School of Biological Sciences, she focuses on synthesising novel peptides. “We take naturally occurring peptides that the body produces, like insulin, and try to improve on them,” she says. “Sometimes they don’t have the right properties to be used as a therapeutic agent, so we change the structure so they’re longer-acting and longer-lasting.”
Brimble’s lab is in the process of getting MedSafe approval to manufacture peptide components for melanoma vaccines. In her second lab, in the School of Chemical Sciences, she and her team synthesise bioactive natural products. Synthetic chemists look to nature – places like shellfish toxins and bacteria that live in extreme environments – for what Brimble calls “beautiful structures” with bioactive properties and then try to replicate them, or improve on them, in the lab.
“Nature may not have provided exactly the right molecule for it to be used as a drug, but it’s very close. We can tinker and play with it to improve the biological profile of the existing natural product to make it even better.” One of the achievements Brimble is most proud of is the development of Rubromycin, a molecule synthesised to mimic a bioactive compound produced by a bacterium that has been shown to have anti-cancer properties.
Brimble leads a team of more than 25 students and post-doctoral fellows and tries to instil in them the lessons she’s learnt over her career – the importance of being systematic, logical and persistent – and the values instilled in her by her grandmother. “She really encouraged me to work hard and persevere. She taught me that things aren’t just handed to you on a plate.” Brimble attributes her success in winning the Rutherford Medal to a consistent and sustained effort and lots of incremental steps along the way. “It’s not like you have a eureka moment overnight and you end up with the Rutherford Medal. That’s not what science is about – it’s about building consistently to reach whatever level you can get to.”