Dame Margaret Brimble is a Distinguished Professor at the University of Auckland, New Zealand where she makes and modifies naturally occurring bioactive compounds from plants, animal tissue, and marine and soil organisms. She has published more than 600 papers and is an inventor on more than 50 patents. Brimble recently spoke with CICNews editor Sharon Oosthoek in advance of her plenary presentation at IUPAC CCCE 2021 in August.

Tell me how your early years helped you become a leader in bioactive natural products and peptides as potential new medicines. I understand your teachers encouraged you to consider a career in medicine – but the horror of being asked to dissect a rat in biology class steered you towards chemistry research.

I didn’t have a great family life so I enjoyed school. I really enjoyed languages – I did Latin and French and German. I was also good at maths, but I didn’t really know chemistry. Our chemistry teacher wasn’t that great at my school but we did biology. My father was a GP and he really wanted me to do medicine. We had to dissect a rat in class and I was the only girl who just couldn’t face it and had to walk out of the lab. I realized then medicine was never going to work for me.

When I went to university, I knew I wasn’t going to do law and I wasn’t really arty. So I just enrolled in chemistry, French and maths and I did a bit of physics too. It was the quality of teaching that got me interested in chemistry – it was really well taught in the first year of university.

I discovered I loved the organization of chemistry, especially organic chemistry. You could just work out a few principles and then you would know how to work out reactions etc. I liked that it was about putting things together in an organized fashion and there was always an answer. It was black and white: what’s the product of this reaction? There was only one answer and there was no wordy justification– it might be this or it might be that. It was either right or wrong and I really liked that.

In terms of finding applications, I never found an application for Latin or maths. But with chemistry I did. I remember going into the first-year labs and making aspirin. I was making something really useful! For me, it all comes down to organic chemistry, the building blocks of life. That’s what got me hooked.

What has been the biggest obstacle in your research career?

I don’t want to come across too negative. I think that puts people off. My first job was at a very small teaching university – an agricultural university. When I arrived, we didn’t even have an NMR to do organic chemistry. We had to get a second-hand NMR and transport it on the back of a truck. But I had some good keen students and was able to start to build an organic chemistry program.

Then I moved back to the University of Auckland where I had been a student myself, and found that it was a challenging experience. I suffered from harassment and bullying. I loved living in New Zealand but the unpleasant job was just too much and after a year and a half I was approached by the University of Sydney in Australia. They were just really, really persistent and I thought, ‘right, I have to give this a go.’

The environment at the University of Sydney was just so much more engaging and supportive. And I’d like to name the person who made me feel part of the team – Les Field. He was my Head of School when I was there. It was him that I wanted to emulate when I later moved back to the University of Auckland.

I was only at the University of Sydney for four years, and then I was  offered the job to come back to the University of Auckland to be the chair of organic chemistry. I wanted to come back home, but it was huge challenge because I walked into a department that was pretty run down.

I built up organic chemistry by introducing New Zealand’s first degree in medicinal chemistry because I wanted to show students the relevance of chemistry. We had all these first year undergraduate students who were trying to get into medical school and when they didn’t get in, they’d go into biomedical science but now they could consider medicinal chemistry as an option.

Some of these pre-medical school students discovered they really liked doing chemistry, but they had to be enticed because they were told if you do chemistry you’ve got do physics and maths which many of them didn’t like.

Chemistry then was biased toward physical chemistry rather than biological/organic chemistry. So in the medicinal chemistry degree the students could also do a lot of biology papers and medicine papers. The medicinal chemistry degree program became popular and students flocked in.

The problem now was that when these students went on to postgraduate degrees we had to pay for the chemicals and it was very expensive. Because of the high cost of freight, chemicals in New Zealand cost double or triple the price compared to the rest of the world and I had to find the money to support our expensive synthetic organic chemistry research program.

So I did a bit of commercial applied chemistry – we worked on trying to develop new rat poisons and agents to treat bovine mastitis because we are an agricultural country. I did this contract research in the background to pay the bills so we could do the fundamental organic chemistry. We have a unique financial model in our university where we pay a lot to use basic instruments like NMR. Now I don’t look back as I have a strong applied portfolio to my research. But it was a challenge and I had to rise to the challenge in a unique way.

You are the first New Zealand woman to be elected a fellow to the Royal Society of London.
And you co-founded the “spin-out” company SapVax to use your peptide lipidation chemistry to generate self-adjuvanting cancer vaccines. Pretty impressive. What are you most proud of?

Our group discovered a drug candidate called trofinetide (NNZ2566) which is now in phase 3 clinical trials for Rett syndrome with Neuren Pharmaceuticals and Acadia Pharmaceuticals. Hopefully at the end of this year, when we get results and if it’s successful – and I say if, because it has a 50% chance – it would be the first drug that’s come out of a New Zealand laboratory and into the market.

What I love about this drug is that it’s for a really debilitating neurodevelopment disorder that affects females. I had a baby late in life. I was 37 years old and I remember having my test for Down syndrome and I remember being really worried. But Down syndrome is nothing compared to Rett syndrome.

I really hope the drug makes it through the phase 3 clinical trials as it will transform the lives of Rett families. If we want to encourage people to do chemistry, I can’t think of a more relevant subject than medicinal chemistry to be perfectly honest. I’d like to go to my grave knowing that trofinetide was born in our lab and was successful.

You are a passionate advocate for female scientists and regularly speak to groups of young women to encourage them to consider science as a career. Tell me about your motivations around this.

I want to make it easier for the next generation. Many of the women I did my PhD with had children and many left the workforce. I’d like to create opportunities for them and see them come back. I have 50/50 males and females in my research group and it is all about creating an environment where everyone can reach their potential and work the hours that suit them. I really want to change the lab culture in synthetic organic chemistry labs.

My daughter likes chemistry but she ended up going to med school. It’s very hard to get into med school but she was determined. In fact, I was prepping her for what she would do if she didn’t get in, but she got in.  She should graduate at the end of this year.

I’m happy to see the biochemistry coming through in her because she really wants to do endocrinology. She loves the logic and basic biochemistry/pharmacology behind endocrinology. I guess some of my genes have made it through to her!