Forget for a moment that former NFL All-Pro Mike Webster was at the end of his life so crippled with dementia that he needed to be zapped with a Taser to get a night’s sleep. Never mind that the NFL suggested Dr. Bennet Omalu, the Nigerian-born pioneer in football-related neurodegenerative research, practices “voodoo medicine.” And put aside that in 2006, the rheumatologist selected by the NFL to lead its concussion research panel co-authored a paper that stated, “mild traumatic brain injuries in professional football are not serious injuries.”
No, the most troubling revelation from Frontline’s chilling expose of the concussion epidemic within professional football was a neurologist's fear that every player in the league may be suffering from a degenerative brain disease brought on by repeated blows to the head.
“I’m really wondering where this stops,” Dr. Anne McKee said toward the end of the two-hour documentary. McKee and her colleagues at Boston University have found the disease in the brains of more than 40 former players. “I’m really wondering, on some level, if every single football player doesn’t have this.”
That may well be the most important of the many questions left unanswered by “League of Denial,” the documentary based on the book by ESPN reporters Mark Fainaru-Wada and Steve Fainaru. But emerging science, and a promising new test, may soon provide the answer.
The two investigative reporters make a compelling argument that the repeated head trauma inherent in football leads to chronic traumatic encephalopathy (CTE), a neurodegenerative disease, and they exhaustively explain how the NFL has spent nearly two decades denying there is a link between the two and trying to discredit the work of respected neurologists like McKee.
Still, the documentary provided more questions than answers for the 85 million self-proclaimed “avid” NFL fans around the world: How prevalent is CTE in the total NFL population? Why does it afflict some NFL players but not others? Is there a genetic factor? How much head trauma must an athlete sustain to be at risk?
Such questions are but one reason the NFL has consistently argued, in the words of Commissioner Roger Goodell, that “the link between football and CTE is unclear.”
Though that seems like an impossibly naive statement, it can’t be entirely dismissed. Concussion research has advanced rapidly since the early 2000s, when the question of CTE in players emerged in the wake of Webster’s death. But it remains an opaque operation. Tau, the corrosive protein that causes CTE, is found only through a microscopic examination of cross-sections of brain tissue after death.
While Boston University’s Center for the Study of Traumatic Encephalopathy has found CTE in 52 of 54(1)(2) brains of former NFL players it has studied, the NFL can point to the response bias inherent in the group’s research. The refrain from the league has long been that the researchers are only receiving the brains of players who are experiencing extreme physical deterioration.
"The problem with diagnosing CTE posthumously is that we're limited to a sample size of people who are clearly having serious neurological issues," said Dr. Robert Cantu, chief of neurosurgery at Emerson Hospital and co-director of the Boston University center. "What we need to clarify the scope of the problem is for seemingly healthy athletes to donate their brains as well.”
That is coming. Hundreds of retired players now suffering from cognitive impairment and premature physical deterioration have agreed to donate their brains to the brain banks at Boston University, the Brain Injury Research Institute and the National Institutes of Health upon their death.
However, the science has until now remained limited by logistics. The test to identify CTE must be done postmortem, as it requires slicing the brain into thin sections, injecting them with dye and examining them under a microscope. The test costs thousands of dollars and takes as long as six months to complete, so the sample size has remained small.
That might be changing. Earlier this year, UCLA researchers published a breakthrough study in The American Journal of Geriatric Psychiatry outlining a method of testing for CTE in living players.
By injecting a radioactive compound into the bloodstream of five retired NFL players, the UCLA researchers were able to identify the biomarkers of CTE in a routine positron emission tomography (PET) scan. The compound, called FDDNP, acts as a tracer by binding with the tau protein deposits associated with CTE. The radioactive chemical tracer then accumulates in the brain in various densities, which show up in clusters of different colors on the PET scan (low-density tau deposits glow blue, while high-density deposits glow red).
It’s essentially a visual map of tau protein deposits in the brain.
All five of the retired players in the study, aged 45 to 73, were found to have high signifiers of CTE. During their careers, they had suffered between two and 20 concussions apiece.
"What this study showed is a pattern of tau deposition in the same areas of the brain that you see in CTE cases in autopsy," said Dr. Gary W. Small, the study’s lead author and a professor of psychiatry and biobehavioral sciences at UCLA. "I want to stress that the diagnosis of CTE, right now, still has to be confirmed after autopsy."
The test, should further research confirm its accuracy and viability, could fundamentally change the research – and the NFL – by providing a real-time picture of the wear and tear repeated head trauma might have on a player’s brain.
The next step in the team's research is to expand the admittedly small sample to thousands of youth, high school, college and professional athletes, then compare the tau levels and symptoms of participants with a myriad of other medical data in order to make connections about the why, when and how tau build-up happens, and more importantly, if the effects can be reversed.
One of the players in the study, 64-year-old former backup quarterback Wayne Clark, gave the UCLA team hope that the presence of tau may not necessarily guarantee a rapid neurological decline.
"Wayne was confirmed to have tau deposition but was not exhibiting serious neurological impairment," said Small. "He seemed to be living a normal life for a 60-year-old. Why? Is it genetic? Is it because [as a backup quarterback] he didn't have as much prolonged exposure compared with his peers? There's a lot to learn."
The demand for this test certainly exists. Researchers say several current NFL players have asked about it, but so far the NFL has kept mum.
"We have already received so many requests for the test from players that it's hard to keep track," said Small. "But we only have so much money available to perform the scans. We are applying for grants from the National Institutes of Health at the moment, but I have not heard anything from the NFL."
Why would the NFL stay quiet? As ESPN reporter Peter Keating said in “League of Denial,” the league favors a “relentless delaying action.” UCLA’s research would force the NFL to face the true scope of its concussion crisis.
Currently, the cost of UCLA’s radioactive tracer, PET scan and accompanying analysis is $6,000. The entire test takes less than two hours. If UCLA’s research holds up to stress testing, the NFL could theoretically finance brain scans for every active player for $9.9 million — 0.1 percent of the league’s annual revenue.
However, Small knows from his two decades researching Alzheimer's disease that the future of his team's CTE research depends not on logistics but on a deeper existential conundrum that the NFL will soon be forced to face.
"All the time, we hear from by people who are concerned that they could have early on-set Alzheimer's and want to come in for a brain scan," said Small. "But right now, we don't have a cure for Alzheimer's disease. So even if we have the answer, what will we do with it? Is the NFL interested in asking these questions?"
That is the billion dollar question.
"Down the line, we may be able to diagnose in real-time — in active, young players — the tau burden on the brain, which we know correlates with brain cell loss," said Dr. Julian Bailes, the co-director of the NorthShore Neurological Institute in Evanston, Ill., and one of the study’s lead researchers. "The question then becomes, is it time to retire?"
UCLA’s research has been criticized in some circles as premature. However, no matter who gets there first, the science to unlock the invisible tracers of neurodegenerative disease is coming much faster than the NFL would like.
This summer, researchers at Germany’s Saarland University published a study in the journal Genome Biology that could lead to a blood test for Alzheimer’s disease, a close cousin of CTE. By identifying differences in microRNA, the tiny fragments of genetic material floating in the blood, the researchers confirm Alzheimer’s with 93 percent accuracy in 202 human trials.
It's not hard to imagine the firestorm that such a test would provoke — from owners, players, agents and fans alike. Imagine, for instance, a potential first-round draft pick is found to have an usually heavy tau burden at a pre-draft screening. What happens next? Does he decide to play? If so, should the NFL let him?
The possibilities that would be opened up by real-time monitoring of the tau burdens on players brains are limitless. Finally, the opaque questions surrounding CTE could be mapped and digested: genetic factors, the threshold of trauma needed to sustain long-term damage, and the most important question of all, what percentage of NFL players have the markers of CTE?
“This research is still in its infancy," said Bailes, "but there are big, tough questions coming that could change the game forever."
(1)UPDATE 10:30 a.m. Eastern 10/10/13: An earlier version of this story overstated the total number of brains examined by Boston University’s Center for the Study of Traumatic Encephalopathy.
(2)UPDATE 3:30 p.m. Eastern 10/11/13: The Boston University Center for the Study of Traumatic Encephalopathy provided us with updated statistics, which we've included here.
