Wednesday, July 14, 2010

Brain, Interrupted - The Scientist

On a sunny Friday, postdoc Suzanne McKenna pulled into a left turn lane in Cary, NC, and stopped, waiting for the light to change. It was time to wrap up a few errands and head home after a long week of work at the National Institute of Environmental Health Sciences. Suddenly, the afternoon hum exploded with a deafening noise. McKenna looked up into her rearview mirror. The front of an SUV was in her backseat. And her head hurt.

In July 1998, McKenna was a workaholic who had recently moved to North Carolina after winning a competitive postdoctoral fellowship from the National Institutes of Health. Only 3 weeks earlier, at the annual meeting of the Endocrine Society, the tall, blue-eyed brunette had presented her work on the responses of estrogen receptors to environmental compounds that mimic the hormone.

But on July 10th, a driver hit the back of McKenna's car going 40 miles (65 kilometers) per hour, without braking. McKenna's neck was thrown forward, slamming her brain against her forehead. As her body recoiled from the impact, the soft brain tissue ricocheted backwards, contorting again as it hit the back wall of her skull. When an emergency worker arrived, McKenna declined treatment and drove her still-operable car home. On the way, she stopped at a friend's house. The friend asked if she was okay. McKenna's eyes looked vacant.

After a few days off, McKenna returned to work, but things weren't the same. She began to spell phonetically. She couldn't remember her phone number or address. At a lab meeting, she was shocked to look down at her notebook to see scribbled numbers and symbols instead of words. "I thought I was going crazy," says McKenna. And her head continued to hurt.

On July 10, 1998, McKenna was one of the 4,700 people who sustain a traumatic brain injury (TBI) in the United States every day—that's 3 people per minute. In Europe, brain injuries cause 66,000 deaths and land 1.6 million people in emergency rooms every year. Overall, 1.7 million Americans suffer a TBI annually, more than the number diagnosed with breast, lung, prostate, brain, and colon cancercombined. In 2009, those five cancer fields received $2 billion in NIH funding. Traumatic brain injury research received just 4 percent of that—$86 million.1

TBI is an epidemic—the number one killer of young adults and children in the US—but it is not a new epidemic. A scant quarter inch of bone and a layer of fibrous membranes protect our brains from sudden trauma caused by a jolt, blow, or penetrating object. TBIs result from falls and car accidents, even an act as simple as a child tumbling off a swing.

Yet for the millions affected by TBI, science and medicine have little to offer. Methods for classifying patients remain rough and antiquated. And there are no effective drugs for TBI: Since the 1970s, not a single Phase III clinical trial has shown a significant benefit.2It's not from a lack of trying, though. From 1980 to 2009, there were at least 27 Phase III trials in TBI. Doctors have tested steroids, hyperbaric oxygen therapy, magnesium, calcium-channel blockers, and other receptor-blocking agents. None showed significant treatment effects.

It's time to pause and step back, researchers say. "We are surrounded by years and years of failure," says Geoff Manley, codirector of the Brain and Spinal Injury Center at the University of California, San Francisco. "When you have 28 failed drug trials based on really good preclinical data done by smart investigators, you can either say none have worked or take a fundamental look around and admit something is going horribly wrong."