This was published 1 year ago
The world’s top melanoma pathologist has brain cancer. Can he save himself?
Australian medical pioneer Dr Richard Scolyer, who was named 2024 joint Australian of the Year on Thursday night, has never used the word “cure” lightly. But in this Good Weekend article from 2023, he described how he was pursuing exactly that.
By Tim Elliott
Dr Richard Scolyer: “I’m not up for palliative care. I want to push the boundaries.”Credit: Tim Bauer
Most people regard the idea of death as final and irrevocable. But in an important sense, each of us is in a constant cycle of death and rebirth. We have more than one hundred trillion cells in our bodies, many of which are dying or being damaged all the time, including by the sun and environmental toxins. For us to survive, those dead or damaged cells need to be replaced in a process known as cell division. Most of the time, healthy cells divide cleanly and efficiently, but sometimes errors occur. If that defective cell evades the body’s immune system, it will replicate, further mutating as it does so, and eventually turn into a tumour.
Early this year, a single cell in Professor Richard Scolyer’s left temporal lobe mutated in exactly this fashion and, unbeknown to him, began multiplying exponentially.
Scolyer, who lives in Sydney with his wife Katie and three teenage children, is tall, lean and fair-haired, with a tendency toward vigorous self-effacement. When he gets excited, which he often does, especially about his work, he sounds like he’s talking in an animated whisper. At 56, he is the world’s leading melanoma pathologist and the most published scientist in the field of melanoma pathology.
As the co-medical director, with colleague Professor Georgina Long, of the Melanoma Institute Australia, he has pioneered world-first treatments, such as pre-surgery immunotherapy and novel drug applications, improving the survival rate for advanced melanoma from less than five per cent 10 years ago to more than 50 per cent today, and saving tens of thousands of lives in the process. Among international melanoma experts who regularly seek his counsel, Scolyer is regarded as something between an oracle and a supercomputer.
In mid-May, Scolyer and Katie were in Krakow, Poland, taking part in a series of research lectures. Afterwards, they drove two hours south to Zakopane, a resort town at the foot of the Tatras Mountains. On their first day they went walking in the mountains, followed by dinner. The next morning, Scolyer woke up feeling out of sorts. “I was nauseated and faint,” he says, when I meet him at his home in Sydney’s inner west. “I then had this sense that I was going to die, like I was losing consciousness.”
He lay on his back on the floor of his hotel room. Katie asked if he would prefer to lie on the bed, but he said no, he was happy where he was. “His symptoms suggested a mild virus,” says Katie, who is also a pathologist. He grabbed a cushion and put it under his head, and told her not to worry, that she should go to breakfast, which she did. She returned 15 minutes later with a piece of dry toast. Scolyer was still on the floor. A few hours later, he attempted to get up. He’d just reached his feet when he groaned, bent over at the waist and pitched forward, falling head first onto the floor. He then began convulsing.
Scolyer was taken to Krakow University Hospital, where he underwent a series of tests, including MRI scans, a lumbar puncture and an EEG. The scans showed a slug-shaped, tumour-like mass in the left side of his brain. Katie sent the scans back to Sydney, to Long and a neurosurgeon colleague of Scolyer’s, Dr Brindha Shivalingam. Five days later, Scolyer was back in Sydney, where he had further tests, including an open biopsy, during which Shivalingam took tissue from the tumour to analyse. Within two days, he’d been diagnosed with an aggressive and terminal form of brain cancer known as glioblastoma IDH wild-type. “It’s the worst of the worst,” says Scolyer. “A straight path to death.”
Doctors have very little to offer patients with glioblastomas. The standard treatment – surgery followed by radiation and chemotherapy – hasn’t changed for 20 years, and remains woefully inadequate. The average survival time is 12 to 18 months; only 25 per cent of patients survive more than one year.
‘This is a one-off opportunity to try something really experimental. So why not give it a crack?’
Dr Richard Scolyer
Shortly after diagnosis, Scolyer made a decision. His entire career had been predicated on trying new things. There was nothing “standard” about the treatments he and his colleagues had developed for melanoma; indeed, they’d transformed the field. So why not use them to treat his brain cancer?
“The stuff we developed for melanoma, the [pre-surgery] immunotherapy, the drug therapies, it’s never been tried with brain cancer,” he tells me. “It could kill me early or it could make what time I have left less enjoyable, and then there’s also a small possibility that I could be cured. But I’m not up for palliative care. F--- that. I want to push the boundaries. This is a one-off opportunity to try something really experimental. So why not give it a crack?”
Richard Scolyer grew up in Launceston, the youngest of two boys. His mum taught kindergarten, and his dad was an auto electrician. On school holidays the family would go camping near Ulverstone, a small town on Tasmania’s north coast.
“We’d go to the beach, swim 10 times a day,” he says. “I can’t believe it now, but we used to coat our skin in baby oil to work on our tan.” When Scolyer’s mother, Jenny, was in her mid-30s, she suffered a series of strokes, and was sent to hospital in Melbourne. Scolyer’s father went along to help her rehabilitate. The boys were sent to live with relatives: Richard, then four, ended up living for nine months on a sheep farm owned by his uncle and aunty. “When Mum came back she was still severely debilitated, and had trouble communicating verbally. I hated seeing her suffer, and it left a big impact on me.”
Scolyer attended Riverside High, a public school beside the Tamar River. It wasn’t particularly academic; most of the boys left in year 10 and did trades. But Scolyer became fascinated by biology and how the body worked. He also liked the idea, as he puts it, “of making a difference to people and how their lives turned out”. By year 10, he’d decided he wanted to be a doctor.
In 1985, Scolyer started studying medicine at the University of Tasmania. He didn’t work especially hard in his first year: he was more interested in AFL, which he played for the university, and later at representative grade for Old Launcestonians.
“The professor of medicine and the professor of surgery both supported my football team,” he says. “I’d go to the ward rounds on Monday morning and all they’d want to talk about is the game.” The university didn’t have many medical experts, but it was good at teaching practical skills: shortly after graduating, in 1992, Scolyer was driving from Launceston to Hobart when he came across a car crash, and ended up intubating people by the roadside.
As a junior doctor, Scolyer worked in cardiology, emergency medicine and paediatrics, all of which he enjoyed. But it was pathology, the study of the causes and effects of disease, that drew him in. “I liked the challenge of using your brain to analyse something and come up with a diagnosis, and I wanted to learn more about diseases.”
‘I was left with this incredible number of virtually impossible cases. The pressure was on.’
Dr Richard Scolyer
In 1998, after training in Canberra and working for a period in the UK, he got a job as a general pathologist at Sydney’s Royal Prince Alfred Hospital before being poached, at the age of 34, by the Sydney Melanoma Unit, a specialist research and treatment centre affiliated with the University of Sydney. (In 2007, the unit was renamed Melanoma Institute Australia.) “He was fresh-faced and bright-eyed,” says the then-director, Professor John Thompson. “He looked far too young to be doing the job, but everyone recognised him as being very astute.”
The unit saw a huge number of cases, some of which were rare and hard to diagnose. “There are some tumours that look benign but are malignant and will kill the patient, particularly in soft-tissue tumours,” Scolyer says.
A week after he started, the lead pathologist went on leave. “I was left with this incredible number of virtually impossible cases. The pressure was on, and I learnt very quickly.” Increasingly, the senior pathologists would defer to his judgment. But the work was dispiriting. Then, as now, Australia had the highest rate of melanoma in the world: in 2000, one Australian was diagnosed with it every hour. (Today it’s one every 30 minutes, according to the Institute.) But the disease was essentially incurable.
“There were no drugs that worked for people with advanced-stage melanoma,” says Scolyer. “The unit would have team meetings, and there’d be a list of patients we’d go through and most of them would die from their disease.”
Surgery was the frontline treatment, but it was a blunt instrument. “They would do something called an excision in continuity, so you’d have the primary taken out, plus a big chunk with all of your lymph nodes. But then, 80 per cent of the time they’d find out that the lymph nodes wouldn’t have any tumour in them, and the patients were often left with complications.”
Former Melanoma Institute Australia director, Professor John Thompson, at right, with Scolyer.Credit: Courtesy of Richard Scolyer
In order to get a more accurate prognosis, the unit, led by Thompson, began using sentinel node biopsy, a new, minimally invasive procedure that allowed doctors to tell exactly which lymph node the primary tumour had spread to. (The Institute is now a leader in the technique.) Starting in 2009, the Institute also began taking part in the first human trials of three promising new immunotherapy drugs, called ipilimumab, nivolumab and pembrolizumab. (Immunotherapy stimulates the body’s own immune system to fight cancer.)
“We were the first in the world to conclusively prove that they worked, and the first in the world to use immunotherapy in any cancer,” says Georgina Long, who joined the Institute in 2009 and became co-medical director in 2017, the same year as Scolyer.) “It was a ‘penicillin moment’ in cancer treatment. We started seeing cures. So we began experimenting with other novel immunotherapy treatments.”
Some of these treatments involved administering immunotherapy drugs in complex and unique combinations. But the biggest breakthrough was neoadjuvant immunotherapy, or the use of immunotherapy before surgery. Previously, doctors removed cancerous tumours as soon as possible, after which the patient might undergo radiotherapy and immunotherapy. (Chemotherapy was ineffective with melanoma, and never used after surgery.)
In 2014, however, the Institute began exploring the possibility of administering immunotherapy before excision. “The idea is like training a drug sniffer dog, if the sniffer dog was your immune system and the drugs are the cancer,” Long explains. “You train them by giving them a large amount of drugs to sniff, then take it away and put a tiny bit in a corner to see whether they can find it. If you try to train the dog on a tiny little bit of drugs, they’re not as clear what they’re looking for.”
The treatment came with risks: the immunotherapy would be given to the patient for up to 12 weeks before surgery, during which time the tumour could run out of control. But the results were groundbreaking. In 2018, the Institute published the first analysis of an ongoing study that showed that giving immunotherapy before surgery – even in people with Stage III invasive melanoma – could almost eradicate the cancer. (The latest results, in 2022, showed that 70 per cent of patients were permanently cured.)
Immunotherapy also worked on melanoma that had spread to the brain. “That was crucial,” says Long. “For 60 years now, people have said that the blood-brain barrier would prevent most cancer-killing drugs from getting into the brain. But we debunked that, totally. We showed that’s not true.”
It was only a matter of time before researchers in other cancer fields began to take notice. “We saw the results they were getting and were amazed and intrigued,” says Michael Boyer, chief clinical officer at Chris O’Brien Lifehouse in Sydney and a specialist in lung cancer. “We thought, ‘If you can do that with melanoma, which is really difficult to treat, imagine what you could do with other cancers.’ And so their approach rapidly spread from melanoma to lung cancer, kidney cancer, and head and neck cancers.”
With colleagues Professor Georgina Long and Dr Robert Rawson at the World Triathlon Championships in Lausanne, Switzerland, in 2019.Credit: Courtesy of Richard Scolyer
If the Melanoma Institute were a football team, every Australian would know about it. Instead, it remains one of the country’s best-kept secrets. The centre, which is headquartered in a purpose-built, three-storey building in Wollstonecraft on Sydney’s north shore, is now the largest melanoma research and treatment facility in the world, with an in-house team that includes surgeons, oncologists, dermatologists, pathologists, researchers and nurses. This collaborative approach has been a boon to patients, who, instead of being bounced around from specialist to specialist, can be treated at every stage of their disease all under one roof.
And more often than not, the patients give back – literally. The Institute has accumulated the largest melanoma biobank in the world, some 628,000 blood, tissue and stool samples, all donated by patients and held in industrial fridges that run at minus 82 degrees. The samples, which are kept in secure locations throughout Sydney, are regularly loaned out to melanoma researchers overseas.
The Institute occasionally receives government grants but is mostly reliant on philanthropy. That it has been built almost entirely on goodwill and hard work is a palpable source of pride for Scolyer and Long, who talk about the Institute as if it were a nursery of rare and endangered plants. “It’s seriously one of a kind,” Scolyer says.
The first time I met Scolyer was in hospital, two days after he’d had his tumour removed. He was lying on a bed, in a white gown, looking weary – and itchy. For the previous two weeks, in the lead-up to his surgery, he’d been given a powerful cocktail of immunotherapy drugs, one of the side effects of which is rashes. The left side of his head was stained bright magenta from the surgical disinfectant, and there was a 15-centimetre incision, covered by a strip of white plaster, running vertically down his temple. But he was perfectly lucid: “It’s amazing I can think after having a big chunk of my brain cut out.”
He wanted to know what I planned to do with the story. “When are you going to run it?” he asked, with clinical candour. “I guess you’re going to wait till I die, right?”
When you think of a tumour, most people picture a lump. But many brain tumours, including Scolyer’s, aren’t like this. They’re more amorphous, with irregular shapes, consistencies and textures. “Some parts of Richard’s tumour were softer, almost liquid, the same as egg white, and then other parts were firmer, like when you get a lumpy bit in the middle of a custard,” says Brindha Shivalingam, who operated on Scolyer in June. “In certain areas it was greyer, and in some parts I saw increased blood vessels which were feeding the tumour.”
Shivalingam used a heat device to cauterise sections of the tumour; the more jelly-like tissue was sucked out through a narrow tube. The only bits she snipped were the blood vessels, which tethered the bulk of the tumour to the brain. Unfortunately, Scolyer’s glioblastoma was in the innermost part of his temporal lobe, with minute tentacles that infiltrated, like tree roots, back into the hippocampus. “I didn’t chase them,” says Shivalingam, who has known Scolyer for 15 years.
“If I went too far, it would have caused major problems in terms of memory, with his ability to find the right words and potentially also some personality issues.” (The fact that it is impossible for surgeons to remove every single cancer cell in the brain is one of the reasons that glioblastomas inevitably come back.)
The surgery took six hours. When the tumour was completely detached from the rest of his brain, Shivalingam lifted it out of Scolyer’s skull with a pair of oversized tweezers, called tumour grippers. It was about four centimetres by two centimetres and vaguely sausage-shaped. The tumour was dissected, with different pieces snap-frozen in vials of liquid nitrogen and sent to the Sydney Brain Tumour Bank at Royal Prince Alfred Hospital, and to the Institute’s biobank in Wollstonecraft. The tumour left a sizeable cavity in Scolyer’s brain, the walls of which Shivalingam coated with immunotherapy liquid.
Georgina Long, a close friend, is co-director with Scolyer of Melanoma Institute Australia. Credit: Tim Bauer
Long and her colleagues set about analysing the tumour. Most importantly, they compared it to the tissue that had been removed from Scolyer’s brain during the initial biopsy, two weeks earlier, before he underwent immunotherapy. Much to their delight, they found that the drugs had indeed worked, multiplying the number of activated immune cells – or T-cells – more than tenfold. Some of these T-cells were subsequently grown in a lab and now sit in bags in a freezer, should Long want to infuse them back into Scolyer’s body later on. The Institute’s lab also sequenced the tumour’s genome in order to produce a personalised vaccine that, if successful, will further enhance Scolyer’s immune response. (The vaccine should be ready in late September.)
“When I saw that huge boost in T-cells, I was, like, ‘Yes!’ ” Long tells me when we meet in the office she shares with Scolyer at the University of Sydney. “It was the best news we could have had.”
Long, who is small and lithe and crackling with energy, met Scolyer in the late 1990s, when she was a medical student at University of Sydney and he was a registrar. They shared an interest in fitness, which they pursued with a near-pathological competitiveness. (Both Long and Scolyer have represented Australia at world triathlon championships, in Australia and overseas.) She has, over time, become one of Scolyer’s closest friends. Long was at home in late May when Shivalingam called to tell her about his diagnosis.
“Using the word ‘cure’ is almost seen as childish because, like, what if it doesn’t work? But now, with Richard, we’re going for a cure.”
Professor Georgina Long, Melanoma Institute Australia
“I collapsed,” she says, putting her hand to her chest. “My kids and my husband came up, and were like, ‘What’s going on?’ But I couldn’t stop crying.”
When Scolyer and his wife flew back into Sydney from Poland, Long and her husband were at the airport to meet them; they drove to Scolyer’s house to collect some clothes, then straight to Royal Prince Alfred Hospital in Camperdown for more tests. At the beginning, the diagnosis seemed definitive.
“There was no bargaining, no denial, it is what it is,” says Long. But she quickly regrouped. The more research she did, the more experts she talked to, the more convinced she became that there were options. “We’ve seen in melanoma how things can turn around,” she says.
Scolyer with his wife Katie and family.Credit: Courtesy of Richard Scolyer
Now, with Scolyer responding to immunotherapy, Long has dared to crack open the door and let a little light in. “Usually, as doctors, we’re not allowed to hope,” she tells me. “Using the word ‘cure’ is almost seen as childish because, like, what if it doesn’t work? But now, with Richard, we’re going for a cure. That’s the blue sky, the ultimate goal.”
Others in the brain cancer field are cautiously optimistic. “Single agent immunotherapy approaches have yielded disappointing results for glioblastoma,” says David Reardon, clinical director of the Centre for Neuro-Oncology at Harvard Medical School’s Dana-Farber Cancer Institute, who is familiar with Scolyer’s treatment. “But Dr Scolyer is being treated with a highly innovative combinatorial immunotherapy approach [for which] there is a strong basis.”
When medical students graduate, they take the Hippocratic Oath, pledging not to harm their patients. Getting a doctor to adopt an experimental treatment, then – one that may involve a higher-than-normal risk to the patient – can be difficult. “Most people are scared to not go down the standard treatment protocols,” Scolyer tells me one afternoon over a cup of tea at his home.
“It took some discussions to get people on board.” This is particularly so with the brain, which, apart from being irreplaceable, is held in an enclosed space. Should anything go wrong and cause swelling, the brain has only one place to go – down into the spinal column. The phenomenon, called “coning”, usually leads to brain-stem death. Immunotherapy also carries the risk of liver failure, especially in combinations as strong as Scolyer’s. (Scolyer had mildly abnormal liver function test results after his first bout of treatment, and they remain suboptimal.)
Scolyer after receiving his AO in 2021.Credit: Courtesy of Richard Scolyer
Scolyer and Long understood these risks better than anyone. But they still had to convince others to get on board. Scolyer and his wife wrote long letters to doctors explaining how the decision to pursue the treatment was his alone and that he was cognisant of the implications. He relied in part on the support from cancer experts he’d worked with overseas, including at Harvard, Stanford and the MD Anderson Cancer Centre in Houston. (When surgeons at MD Anderson heard about Scolyer’s diagnosis, they bought him a new flat-screen TV to help distract him during treatment.)
From the moment of his diagnosis, Scolyer regarded his situation as a unique opportunity to do further research into brain cancer. “I’m a guinea pig,” he tells me with a degree of relish. In order to gather data, then, he has submitted at every step of his treatment to a range of additional procedures, the first of which was his open biopsy, in early June. (The open biopsy, which involved cutting open the skull and exposing the brain, allowed doctors to gather more tumour tissue for testing, but involved a greater risk of injury than the usual core biopsy, which is performed with a needle.)
Scolyer has also had ongoing neurocognitive tests and a regular schedule of lumbar punctures. “I’ve had four so far,” he says, sighing at the thought of it. A lumbar puncture, also known as a spinal tap, is a diagnostic tool that involves sticking a needle into your spinal column and withdrawing cerebrospinal fluid (CSF). “We’re trying to see if there’s a biomarker in my CSF that would indicate if there is a recurrent tumour.” At present, the main way to check for recurrences is radiology, but it can be inconclusive. “If this [lumbar puncture] method proves more accurate, it could revolutionise treatment.” Lumbar punctures are, however, notoriously unpleasant: the last time Scolyer had one, some of his cerebrospinal fluid leaked out. “You get headaches from it, which can make me a bit irritable.”
‘Richard struggles from time to time. He tells me, “I’m too young to die. I’m not prepared to die.” ’
Professor John Thompson, former Melanoma Institute Australia director
Some of this research is already paying off. In early August, Scolyer announced that, based on the data from his immunotherapy, two biopharmaceutical companies are looking at expanding drug development programs into glioblastoma, mainly based around T-cell therapies. Another company has volunteered its drugs for further research into pre-surgery immunotherapy in glioblastoma. “Irrespective of whether it changes my life, it’s already clear that we’ve broken open the whole glioblastoma field,” Scolyer says.
Scolyer describes himself as “fairly quiet, definitely not an extrovert”. He has from the outset, however, been open about his condition, granting multiple interviews and posting updates on Twitter and Instagram. This is partly for convenience: “At the beginning I got bombarded with messages, so it just seems easier to let people know what’s going on this way.” He also hopes the publicity will boost awareness of brain cancer and new treatment opportunities. His family was also a factor. “I thought, if I’m going to die, my kids are still relatively young, and even trying to remember what happened 10 years ago can be a struggle.” Documenting his experience, then, is “partly driven by me creating a legacy for my children, to be able to look back on what’s happened to me”.
Scolyer’s default setting on social media is relentless optimism. (His Insta clips invariably open with a jaunty “Hello everyone! Richard Scolyer here!“) But according to his friend and former Institute director, John Thompson, he’s as afraid as anyone. “Richard struggles from time to time. He tells me, ‘I’m too young to die. I’m not prepared to die.’ ”
One day, at his home, Scolyer got talking to me about his children. “They’re basically the same as they were before my cancer. They get annoyed at you for saying or doing something, just like they normally would. Or occasionally, I’ll be a bit sad, and they’ll come and comfort me.” In general, he finds it best not to dwell. “You could feel sorry for yourself and sit at home and not engage in your life. But that doesn’t feel right to me. It’s not what I want to do. I want to keep contributing.”
“You could feel sorry for yourself and sit at home and not engage in your life,” says Scolyer. “But that doesn’t feel right to me. It’s not what I want to do. I want to keep contributing.”Credit: Tim Bauer
Scolyer had his final session of radiotherapy in late August. He celebrated by going on a 12-kilometre run. His hair was a bit thinner and his skin a bit paler (radiotherapy can cause anaemia), but he otherwise felt okay. A couple of days later, however, he had a small seizure. His scans came back clear, and Long thought it could have been due to fatigue. When I first met him, he told me that this might happen, that although he was feeling fine at the time, he could spiral down with little warning. Whether this seizure was the beginning of a downward turn was difficult to say.
In the meantime, he continues to work. He goes into the Institute, and to a lab that the Institute operates at the University of Sydney. “It feels right that since I’ve lost a large bit of my brain, it’s a good idea to keep the rest of it as active as possible,” he says. The neurocognitive tests aren’t showing any memory deficits, but he’s not telling his kids that. “Sometimes, if I can’t remember something and the kids get angry, I just blame it on the tumour.”
And, of course, he’s still exercising. It’s impossible for him not to. Standing still doesn’t suit him. He needs to keep moving, to be looking forward. “Running makes me feel euphoric,” he says. “I want to get more of that. I’m not willing to give up on my life yet.”
Hear Richard Scolyer discuss his high-stakes treatment for brain cancer with colleague Georgina Long on Good Weekend Talks.
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