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But the view was wrong. Dr. Weiss and Dr. Reynolds repeated their accidental experiment “100 times to convince ourselves.” But it looked like proof to them.
The journal Nature turned it down in 1991, saying “it was not of general interest.” But after a few more experiments, Science accepted it in 1992. The report turned medical dogma on its head, proving that the adult brain does not lose the power to make new cells.When Dr. Dirks went back and read the Calgary paper, he knew he'd found the way: The growth factor used to coax the growth of normal adult brain stem cells could perhaps be used to induce brain-cancer stem cells — if they were there — to grow.
Typically, researchers had cultured cells from the brain with bovine serum, a nutrient derived from cow blood. But Dr. Dirks said adding the serum actually prompts stem cells to mature and stop growing.
From the tissue of surgically removed brain tumours, Dr. Dick was able to use a growth-factor cocktail and found that were indeed abnormal stem cells present. These carried the protein CD133 on their surface, the same marker now identified on abnormal stem cells in both prostate and colon cancers.
Dr. Dirks found that that 100,000 ordinary cancer cells cannot grow a brain tumour in a mouse. But as few as 100 to 1,000 cancer stem cells can reliably give rise to the disease.
But as with Dr. Weiss, Dr. Dirks found that publishing what he'd found turned out to be nearly as tricky as discovering it.
“I really had to shop it around,” he said. After taking six months to consider it, Cancer Research published the report in August 2003.
During that time, stem cells was suddenly becoming a hot field.
In April 2003, Michael Clarke at the University of Michigan, who had worked with John Dick on a leukemia experiment, and Max Wicha reported that they had identified the breast cancer stem cell. Using mammary tissue taken from cosmetic breast surgery, they identified that only a tiny fraction of abnormal stem cells were the drivers of those breast tumours.
“That had definitely created a buzz,” said Dr. Dirks, who reconfirmed his finding of a brain cancer stem cell in a live animal model. Three other groups later reported the same discovery.With abnormal stem cells detected at the roots of blood and two solid-tumour cancers, the research field was suddenly forced to take notice. Some scientists began the search for stem cells in their own specialty cancers. Others began to debate their importance.
“There was a meeting around 2003, 2004, where a heated debate broke out about the cancer stem cell hypothesis,” said Jeremy Rich, a neuro-oncologist at Duke University in North Carolina. “It tended to be divided among proponents and skeptics and the more senior the researchers the more likely they were to be skeptical.”
As Dr. Wicha put it: “To people who have devoted their life to chemotherapies and shrinking tumours, this really still has to be proven. Until you show it in people, they are going to be skeptical.”
Dr. Rich said he himself was a skeptic. But after “the elegant work” of Dr. Dirks, he went to stem-cell biologists at Duke (who happen to be a group of Canadians) and began his own experiments. One of them showed brain cancer stem cells can resist radiation.
Dr. Dick divides his time these days between international meetings, the news media and the busy work of his lab.
Peers in his circle say he has been wooed to take up directorships, run institutions. Dr. Dick, however, has “fought it tooth and nail,” never wanting to be too far from the actual science.
Last weekend, his group and another in Italy pinpointed abnormal stem cells as the source of colon cancer. The two reports were both published in advance by Nature. But Dr. Dick said he hasn't even had time to buy a good champagne for the lab team.
Not that there's room on the ledge.