If you're looking for the roots of the furor over concussions in football, you'll find them inside the brain bank at Boston University.
Over the past five years, researchers there have studied the brains of dozens of ex-football players, from former National Football League stars like Junior Seau and Dave Duerson to some who never played beyond high school.
All had a couple of things in common: They had taken years of big hits on the football field, often suffering multiple concussions. And all had either committed suicide after bouts of depression or died in old age in a state of dementia.
After putting thin slivers of the men's brains under microscopes, Boston researchers saw that their neurons had become stained brown by a tangle of proteins called tau.
It was the telltale signature of chronic traumatic encephalopathy, or CTE. The degenerative disease had long been associated with boxers — the reason aging boxers were sometimes termed "punch-drunk" — but it had never been linked on a large scale to football players.
The Boston researchers' theory: that repeated head trauma in football produces permanent brain tissue degeneration, leading to a progression of depression and severe cognitive decline.
The fallout from the Boston research has been immense.
The NFL changed its rules in an effort to prevent concussions and required teams to change how they handle the injuries. Just last month the league settled, for $765 million, a lawsuit filed by former players alleging past inattention to brain injuries.
Football at all levels has been forced to change. Most states have passed laws requiring more care in how concussions are handled in youth sports. The NCAA has required schools to come up with concussion plans, though it's facing criticism and litigation for not doing more.
Those who back the research say more reforms are needed.
"We are not trying to kill football," said Chris Nowinski of the Sports Legacy Institute. "But we certainly want to change football."
Still, despite everything that research has ushered in, it's surprising how little has actually been proven when it comes to football, concussions and long-term brain damage. An international panel of concussion experts meeting in Zurich last year concluded it remains only speculative that football hits cause CTE.
"The results we have linking concussions and CTE are weak and wouldn't be used (to explain) any other disease process," said Andrew Peterson, a doctor who directs the University of Iowa athletic concussion program.
The brains studied to date have come from a highly selected population of former players who had exhibited obvious symptoms of CTE before death. To learn the true risk for the disease, researchers would have to study a large number of brains from players who died under all circumstances.
Thousands of former football players have had long college and pro careers without ever exhibiting signs of CTE, suggesting it takes something more than multiple big hits to induce the disease.
Is genetics a factor? Researchers don't have the answers.
"The implication is everyone ends up like Junior Seau, and that's absolutely not true," said Stefan Duma, a Virginia Tech bioengineer who has studied football and concussions. "If you look at the numbers, it's a big stretch to say everyone who plays football will get CTE."
Former Nebraska football coach Tom Osborne coached well more than 1,000 players during 25 seasons in Lincoln. Hundreds of those Cornhuskers likely suffered concussions. He said he has yet to hear a former player talk of experiencing CTE-like symptoms.
Boston University officials acknowledge the shortcomings of the research. But Nowinski said the lack of a fully conclusive link should not stop efforts to reduce concussion risk.
"The more research we do,'' he said, "the more we find brain trauma in football is not benign."