The first sign of the disaster that was about to befall the Graham family came in the form of a phone call on a school day in May, 2019.
Thomas Graham’s wife, Cindy, had failed to pick up the couple’s twin boys, an out-of-character lapse for the devoted mom.
Mr. Graham raced to the family’s home in Guelph, Ont., where he found his wife in bed, unsure of the time or where she was. Part of the house was trashed. The couple later surmised that Ms. Graham had thrashed about while having a seizure.
“For the first week, we thought she had a stroke,” Mr. Graham said. “In hindsight, that would have been so much better.”
Doctors diagnosed Ms. Graham with glioblastoma, a type of brain cancer so lethal that a neurosurgeon warned Mr. Graham against Googling it before his wife’s pathology results came back.
Ms. Graham lived for another 20 months, longer than most glioblastoma patients. During that time, she and her family made a decision that will ensure Ms. Graham lives on in a way that could help medical researchers develop better treatments for glioblastoma.
After her death on Feb. 24 at the age of 47, Ms. Graham’s brain and spinal cord were donated to the Sheila Singh Lab at McMaster University in Hamilton. Researchers there had already collected tissue from three of Ms. Graham’s tumours; every time surgeons cut the cancer out, it grew back.
Taken together, Ms. Graham’s donations offer Dr. Singh and her colleagues an unprecedented opportunity to create a comprehensive biologic and genetic map of glioblastoma, an early but crucial step on the road to treating the insidious tumours.
“We hope to present to the world a body of knowledge that has never been published,” said Dr. Singh, who is also the chief pediatric neurosurgeon at McMaster Children’s Hospital and the head of neurosurgery at Hamilton Health Sciences.
Ms. Graham’s brain held so much scientific promise that McMaster reopened its anatomy lab at the height of Ontario’s second pandemic wave in February to receive the gift. Hers was the only body the lab accepted in 10 months.
“It was such a black time,” said Bruce Wainman, the director of anatomy at McMaster. “We just dropped everything to make sure that this would happen.”
Dr. Singh said Ms. Graham’s donation is particularly important because of the intractability of the disease. Best known to Canadians as the cancer that killed Tragically Hip frontman Gord Downie, glioblastoma is almost uniformly fatal.
Progress on prevention, early detection and treatment of glioblastoma has been stalled for decades. The five-year survival rate barely budged from 4 per cent in the mid-1970s to about 7 per cent in the early half of the 2010s, according to a recent study using data from the United States.
Glioblastoma is a formidable enemy because the tumours are made up of many different types of cells that spread aggressively in the brain, Dr. Singh explained. They also mutate in response to chemotherapy and radiation. When a glioblastoma grows back after an initial operation, as it invariably does, the new tumour is different from its predecessor. The tumours also differ markedly from patient to patient.
Scientists would have a better chance of developing effective drug cocktails — off-the-shelf or tailored for individuals — if they had a more comprehensive understanding of how glioblastomas recur and spread, something that is hard to divine from small tissue samples of primary tumours.
Think of a glioblastoma-afflicted brain as a continent, Dr. Singh said. “When I, as a surgeon, sample a tiny piece of South America, all I’m giving to my lab is Rio de Janeiro ... now they think all of South America must look like Rio de Janeiro, but it doesn’t.”
With Ms. Graham’s brain, spinal cord, blood and tumour samples, Dr. Singh and her colleagues plan to spend the next few years studying the complete terrain of glioblastoma and testing potential treatments on mice genetically engineered to grow tumours like the one that killed Ms. Graham.
The Graham family did not know all that would be possible when they proposed the donation to Fred Lam one day in early January of this year. At the time, Dr. Lam was a clinical scholar dividing his time between Dr. Singh’s lab and treating brain cancer patients, including Ms. Graham.
“This was the first time I had a patient request to donate their organs for research,” Dr. Lam said. “I was lost for words.”
Mr. Graham, a professor of environmental sciences at the University of Guelph, said he and his wife made the offer in hopes of helping others avoid their family’s fate.
In the year-and-a-half after her diagnosis, Ms. Graham went from a warm, funny, talkative mother and scientist – before having her twins, Dean and Darwin, now 8, she worked in pharmaceutical research and for companies that ran clinical trials of new drugs – to someone unable to walk or speak more than a few words at a time.
She used a cane, then a walker, then a wheelchair.
“She just slowly went away,” Mr. Graham said. “There was nothing left unsaid. We loved each other and we communicated well. But it kept stealing stuff from her and us.”
By the time she died in Mr. Graham’s arms at a hospice in Guelph, the cancer had ravaged her brain. The extent of the damage shocked even the doctors and researchers who processed the organ at the anatomy lab a few hours after Ms. Graham’s death.
The brain looked nearly normal from the outside, but when Dr. Lam sliced it open, its healthy pink exterior gave way to the yellowish tissue and ropey blood vessels of a tumour that had invaded nearly half the organ.
“As soon as we cut it open, the room just went silent,” said Sabra Salim, a graduate student in Dr. Singh’s lab.
That night, she went home and locked herself in her room. She was still rattled at seeing up close the devastation wrought by glioblastoma. “I almost felt bad that I felt that way because I was like, ‘I feel that way?’ Just imagine her family.”
That thought made Ms. Salim and her colleagues especially dedicated to getting the most out of Ms. Graham’s gift. The team had hoped to grow as many as 10 cell lines from different parts of the tumour and surrounding brain tissue, which would make the donation a renewable resource for future studies.
For the first month, the cultured cells refused to grow. Ms. Salim and the team decided to cross their fingers and give the cells another week before giving up and freezing them in liquid nitrogen for storage.
Ms. Salim was dreading taking that step when, one day in the spring, “I just looked in the dish and the cells grew. I jumped for joy. Literally, I was like, ‘They’re growing!’ And it was all of them.”
The Graham family has established a memorial research fund in Cindy’s honour to pay for further research into glioblastoma at McMaster.
“If she was here,” Mr. Graham said of his wife, “she would have done that and more.”
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