A not-so-young scientist tells us the story of his success at the famous exhibition and the career it opened up for him.
Donald McDonnell likes to talk. When he starts to answer a question, there’s always an interesting story or two by way of digression before we get back to the topic at hand. This gift of the gab isn’t just useful at parties, however. The ability to tell an engaging story, McDonnell thinks, is fundamental to success as a scientist.
In McDonnell’s case, his successful career started nearly half a century ago when he won the 1978 Young Scientists Exhibition (now the BT Young Scientist and Technology Exhibition).
McDonnell can’t say enough good things about the exhibition. There are very few opportunities like it, he says, for teenagers to develop an understanding of the scientific process.
“It’s the experience of actually coming up with an idea, formulating a hypothesis, doing the research, analysing it.”
Not only that, but one of the most important aspects, McDonnell says, is the storytelling skills it develops – it teaches students how to present their research to an audience who are not experts in the field.
McDonnell has worked at Duke University in North Carolina for about 30 years, where he is, among many other things, Glaxo-Wellcome distinguished professor of molecular cancer biology in the School of Medicine, and runs a lab that develops drugs for breast and prostate cancers.
Image: Donald McDonnell
He tells the story of how he ended up in cancer research.
McDonnell wanted to be a marine biologist when he was growing up. His project for the Young Scientist was about the biological impact of pollution in the River Shannon in Limerick. After his success at the competition (and he went on to win the European Contest for Young Scientists too), he was offered a scholarship from the Limerick Harbour Commissioners on condition he study marine biology at the University of Galway.
Though he had originally planned to study at Trinity College Dublin, this suited McDonnell because he had what he jokingly describes as a “hormonal problem” – his girlfriend Mary, now his wife, was living in Limerick, which was much more accessible from Galway than the capital.
He had met Mary at a dance which, he says, she only attended because her mother, Mrs Downes, had just been diagnosed with breast cancer and her parents wanted some time to themselves. While he was at university, Mrs Downes would ask McDonnell about new treatments, and he would look up papers in the library for her. He soon found that he was more interested in this research than his coursework. Sadly, Mrs Downes died a short time later and McDonnell determined that cancer research was where he could make a difference.
Coming to America
So, McDonnell switched to studying for a BSc in biochemistry. He then planned to head to Stanford University in California to study for his PhD (and had sold Mary on this adventure) but instead went to Baylor College of Medicine in Houston to study under the supervision of his now very close friend Bert O’Malley (there’s a story behind the change of heart involving his Galway professor, his dad and a pint in Durty Nelly’s).
McDonnell describes this time, the early 1980s, as “the advent of molecular biology”. For his thesis, he studied the vitamin D receptor, which is vital for bone, teeth and muscle health, with the aim of defining the mechanism by which it worked. He published a paper in Science in 1987, which he says, “really set me off”.
“It was my first flagpole in the ground that I’m now a cancer researcher.”
With a little nudge from O’Malley, McDonnell set out to find his own niche area of research and this is where his interest in drug discovery really blossomed. He spent a “career-changing” year in Philadelphia at what is now GlaxoSmithKline. By this stage, he and Mary had a young son and they made the move so that McDonnell could learn all about the methods and jargon of drug discovery.
This was followed by a brief stint as an assistant professor back at Baylor. However, after a lunch meeting that was extended because of a storm, the family were once again packing their bags – this time so that McDonnell could join a pharma start-up. “All I remember is that at the end of that three hours, somehow I was moving to San Diego.”
It was a brave move to leave a tenure-track position for a start-up on the other side of the country. This bravery McDonnell attributes to the support of his wife Mary, who was on board for every decision, even now with two young sons to think about. (McDonnell is clearly a proud dad – mentioning his sons throughout our conversation).
It wasn’t long before McDonnell was drawn back to academia, however, and in 1994, he joined Duke University, where he’s stayed ever since.
Research highs
At Duke, which McDonnell describes as having a close-knit vibe that reminds him of Trinity, his focus has been on developing drugs for metastatic breast cancer and prostate cancer.
One of the big breakthroughs he worked on was the development of an assay for the oestrogen receptor, which is expressed in more than 75pc of breast cancers and is therefore a primary target for drugs. The assay allowed for an exponential increase in the number of compounds that could be tested to find potential drug treatments. “It was rocket science in the 90s,” McDonnell explains.
A couple of years ago, his lab had a drug approved for metastatic breast cancer – it’s called Orserdu in Europe. Though he has worked on numerous projects over the years, McDonnell describes this as the “pinnacle” of the lab’s work. The team are currently working on another drug for breast cancer that is in phase 3 clinical trials, which McDonnell hopes will be approved next year.
As for now, the technologies making the biggest difference in the field, according to McDonnell, are CRISPR gene-editing (“That is a gamechanger,” he says) and artificial intelligence (AI) – he mentions AlphaFold and their model which predicts the structure of proteins in minutes, a process that could take researchers months or years to do in the lab.
Only a tiny percentage of proteins are what McDonnell explains as “classically targetable”.
“With the advent of CRISPR and AI, we’re now taking proteins that were classically non-targetable and maybe we’ll target them.”
He’s really excited about what the future holds with this new tech – “There’s incredible progress being made”.
“We’re now talking about the word ‘cure’ for metastatic breast cancer.” This would not have been the case even a few years ago, he says.
A not-so-young scientist
McDonnell shows no signs of slowing down. He has spun out several companies over the years and his latest is called Adara Therapeutics (named for Adare where he and Mary got married), which focuses on drug development. Though he will retire at some point, he says, because taking risks and thinking outside the box is a young person’s game.
Speaking of young people, does he ever get back to judge the Young Scientists exhibition? He has been a judge remotely for some of the categories, but the timing of the exhibition always clashes with a major annual meeting of researchers in his field. He’d go back “in a heartbeat” if the timing works out, he says.
A few years ago, McDonnell was awarded the St Patrick’s Day Science Medal, which recognises outstanding contributions to science and technology from the Irish diaspora in the US. He was awarded alongside fellow Young Scientist winner, Patrick Collision and his brother John, who founded global fintech Stripe.
McDonnell said it was a “very interesting” event, and he spent the entire day with the Taoiseach Micheál Martin, TD.
Martin asked McDonnell what scientific programme he’d put in place if he had the chance. Taking his opportunity, McDonnell made the case to revive a Government-sponsored internship that he had been involved with. It funded university students to get hands-on lab experience at prestigious labs in the US, something McDonnell says is lacking in many science and engineering degrees in Ireland nowadays, partly due to university funding cuts.
McDonnell hosted many students in his lab. He says the work was hard but hugely beneficial to the students, who all went onto further study. The programme was cut during the recession in the 00s but McDonnell would love to see it brought back.
Martin met this suggestion with “fantastic enthusiasm”, McDonnell says. Though, unfortunately, he has never heard any more about it.
This brings McDonnell back to the Young Scientist exhibition and the value of getting practical experience of the scientific process at a young age. “Anything that provides students with research experience is positive.” A storied career under his belt and yet McDonnell still hangs his 1978 certificates in his office – positive indeed.
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