RACHEL PERRET Drug designer
It started with Louis Pasteur and a syringe of little soldiers. Rachel Perret pulls a children’s picture book from the shelf in her office at Wellington’s Malaghan Institute of Medical Research.
Called The Value of Believing in Yourself ,it tells the story of Pasteur’s discovery of the rabies vaccine. The horrible little rabies viruses were hiding in the gloom where no-one could find them, so Pasteur made an army of magical soldiers (neatly packaged in a syringe) who could see in the dark and fight them off.
The young Perret who devoured that book wanted to be a doctor. She shadowed a pathologist and paediatric oncologist around Christchurch Hospital and marvelled at the bravery of the children as they suffered through chemotherapy. There was something about cancer – the injustice of a disease that took the young with the old, a traitor that turned the body against itself.
But when she got to Otago University to study medicine she discovered she was useless at remembering bone structures and blood vessels. And shyness stood between her and patients. So instead she took the path of scientific research.
‘‘I liked the idea of designing and discovering the cures rather than administering them to the patients.’’
Now, at 41, she’s leading a team at the Malaghan trying to fit out their own little army of soldiers to battle blood cancers.
Before January, Perret was working at Fred Hutchinson Cancer Research Center, the Seattle institute where a Nobel Prize winner invented bone marrow transplants. Her mentor was a world-leading pioneer in using the immune system’s T-cells to fight cancer. A few years back, Amazon founder Jeff Bezos slipped them a handy US$35 million.
So why leave? It’s a good question, Perret concedes. She didn’t want to leave her research project, but she wanted to come home. She missed steak and cheese pies. Oh, and it was a chance to do groundbreaking research to bring new cancer treatments to New Zealanders.
Perret’s research team will work alongside the Malaghan team trialling engineered T-cells against non-Hodgkin lymphoma in patients who have run out of options. The ENABLE trial hopes to test the treatment’s safety in up to 12 patients.
Her job is to find ways to make the therapy better and to work out whether the technique can also be used in solid tumours, such as those that grow in lungs, breasts and the brain.
T-cells are the new big thing in cancer treatment. They’re the immune system’s frontline response – the soldiers that search out and destroy marauding nasties.
But T-cells have a kind of lock and key system – they need the right receptor or protein to recognise the cancer, latch on and unlock their killing potential.
In Seattle, Perret was extracting T-cells from donated blood from healthy patients, testing their reaction to the cancer and copying the receptors of those T-cells that hold the key to the cancer’s lock.
The patient’s own T-cells are then reengineered to include the natural receptor that allows them to recognise – and destroy – the cancer. The only problem with that strategy is that receptors have their own tissue signature, so it’s not a one-size-fits-all. Like organ transplants, you have to match the person to the receptor. It’s a kind of semi-personalised treatment, that comes with a significant price tag.
‘‘A pharmaceutical company can make drugs on an assembly line and can use machines for most of that. For cell therapy you need highly trained technicians to take care of the cells, which are very finicky and precious and have to be babysat daily and watched. So that builds up the cost.’’
The difference with the work Perret is now doing with Malaghan is that instead of copying the T-cell receptors of healthy people, they’re manufacturing artificial ones, called chimeric antigen receptors (CAR).
Perret says the hope is that the CAR T-cell receptor will be stronger than the natural version at latching on to and destroying the cancer. Part of her job will be to see if they can improve the effectiveness of the T-cells, and to see whether the concept can be extended to solid tumours.
At present, the focus is on blood cancers, as they are easier for T-cells to target. Treating solid tumours would require teaching the T-cells better navigation skills.
‘‘Solid tumours like lung or prostate, they are sort of walled off in their own little microenvironment, where they have a whole balance of chemicals and cell types and structural mechanisms in place to isolate them off to protect them from the immune system and protect them from attack. So it’s more challenging to get our T-cells into those kinds of tumours.’’
Perret’s parents emigrated from Switzerland to Christchurch in the 1970s, so she grew up speaking French. That and skiing. She was two when they stuck ski boots and planks on her feet and she cried when they took them off. She didn’t know left from right so her instructor named one leg Bert and the other Ernie.
So after finishing her degree, she did an OE in Switzerland, ski instructing, babysitting for cousins and working part-time in a drug company lab.
She caught the immunology bug, so to speak, from Otago University professor Margaret Baird. It was Baird who suggested she do her doctorate at the Malaghan Institute.
For her post-doc, she returned to her parents’ home town of Lausanne, to the Ludwig Institute of Cancer Research, to study vaccine responses. It was fascinating work, but she longed to be involved in research that was closer to being tested in humans. That’s how she ended up working under top T-cell immunotherapy pioneer Phil Greenberg, at Seattle’s Fred Hutchinson Center.
Greenberg’s career trajectory shows the patience needed by lab scientists, Perret says. It’s not a glamour job, with long and exhausting days in the lab, mostly resulting in depressingly negative results.
‘‘I don’t know that there were many eureka moments. It was more: hard slog, hard slog, hard slog – oh my goodness, a result, finally!
‘‘It’s hard when you want to be curing people who have cancer to know that these processes can take 5,10, 20 years. My mentor in the US I think has been working on this for more than 40 years. He’s starting to see results now. So knowing if you wait long enough and work hard enough, the results will be there in the end is a way to maintain your patience – if it starts to fray at the edges.’’
While Perret loves her job, being a research scientist is increasingly competitive, with more and more people completing science PhDs and senior researchers sticking around longer, creating a bottleneck for those trying to enter the profession.
And sexism remains. While biology is less male-dominated than other science areas, and the Malaghan has more female staff than male, she has still felt she was taken less seriously by male scientists. However, when she finally got around to asking for the promotion she deserved there was no dispute. ‘‘I should have been braver,’’ she says.
Perret was supposed to be attending an international conference in March, before Covid-19 scuppered those plans. That’s one of the perils of working at the end of the world – there are fewer opportunities to mix with others doing similar research. You also have to be super organised, as lab supplies that would turn up the day after ordering in Seattle take weeks or even months to arrive here.
There is also another tradeoff to her Wellington harbour view: ‘‘It’s windier than I remember.’’
‘‘I liked the idea of designing and discovering the cures rather than administering them to the patients.’’