New device shows that brain injury may linger even after obvious symptoms disappear.

MIT Technology Review, August 4, 2010, by Emily Singer  —  Football players who suffer a concussion on the field may not have fully healed even after their outward symptoms, such as memory or balance problems, have disappeared. The findings come from a study of nearly 400 high school and college football players using a new portable device for assessing brain injury.

Researchers hope the findings, and some form of portable brain-monitoring device, will help physicians determine when it is safe for players to return to the field.

“There has long been speculation that even after symptoms resolve, there is a period of vulnerability at which the brain has not completely healed,” says Michael McCrea, a neuropsychologist at Waukesha (WI) Memorial Hospital, who led the study. “This study provides some preliminary support for that theory.”

Last fall, the National Football League instituted new rules requiring players who have suffered head trauma to get permission from an independent neurologist before returning to play. Diagnosing brain trauma accurately is difficult. Also, while the issue is still controversial, many scientists and physicians think a blow to the head while the brain is still healing from an earlier blow might significantly worsen damage, especially in the long-term.

The danger of repeated concussions has become a major issue in professional football, thanks to a number of high-profile cases of ex-players suffering early dementia and severe psychological problems. Autopsies of at least six former professional players who donated their brains to research revealed chronic traumatic encephalopathy, a degenerative brain disease caused by head trauma.

An estimated 1.6 million to 3.8 million sports-related traumatic brain injuries occur each year. One of the biggest challenges in studying concussion, and both the long-term and short-term effects of repeated concussions, is finding a reliable way to assess brain injury. The damage that results from concussions is typically too subtle to be detected with traditional brain imaging technologies. So physicians diagnose it based on characteristic symptoms, such as nausea and headache, as well as through cognitive and neurological tests.

Many football players, eager to return to the field, also underreport injuries and their symptoms. According to anonymous surveys of football players, about 50 percent sustain a concussion during the season, many more than are actually reported, says Chris Nowinski, president of the Sports Legacy Institute, a nonprofit organization based in Waltham, MA, that studies brain injury in athletes. A noninvasive, simple device that could be used immediately after the injury occurred would provide a way to objectively measure a player’s symptoms.

Electroencephalograph (EEG) is a decades-old technology that measures electrical activity in the brain from the surface of the scalp. But using it to study mild traumatic brain injury has been a challenge, in part because the technology is highly susceptible to noise, such as head movements, and it must be performed by a trained expert.

Recently companies have developed more robust, portable devices, thanks to new sensors and advances in the algorithms used to process the data they collect. Such devices also require less training for those who use them. BrainScope, a startup based in Bethesda, MD, has developed one such device, which it is testing for athletic and military applications.

In the new study, McCrea and collaborators used the BrainScope device to analyze brain activity in nearly 400 football players at the start of the season to determine baseline brain activity. Twenty-eight of those players sustained a concussion during the study period. These players had their brain activity measured again right after the incident, as well as days later. Scientists also gave the players tests currently used to assess concussion, including tests of cognitive function and balance. They then compared changes in brain activity in injured players to both noninjured players and nonathlete controls.

“It turned out that symptoms, cognitive function, and balance had all returned to normal within the first week after a concussion,” says McCrea. “But brain electrical activity remained abnormal at day eight.” Brain activity returned to normal a month and a half later, when the next measurement was taken. McCrea says they now plan to repeat the study, assessing brain activity after two weeks to get a better handle on when the brain returns to normal. The findings, published this month in the Journal of Head Trauma Rehabilitation, suggest that the brain’s “vulnerability lasts a bit longer than we thought,” says Ross Zafonte, a physician and scientist at Spaulding Rehabilitation Hospital in Boston. Zafonte was not involved in the study.

At this point, the BrainScope device is still a research tool, rather than a diagnostic one. It’s not yet clear whether it can diagnose an individual case of concussion; in the newest study, researchers added together brain activity profiles, rather than comparing before-and-after profiles of individual players. “I do think there are EEG abnormalities, but I don’t know how specific or reliable they are,” says David Hovda, director of the Brain Injury Research Center at the University of California, Los Angeles. Hovda was not involved in the study.

It’s also unclear what the abnormalities in brain-injured players really mean–doctors don’t understand exactly what’s happening in the brain after such an injury. “Detecting an abnormality is something we’re good at, but linking it to a clinically meaningful situation is different,” says Zafonte.

Genetically modified bacteria can produce enough proteins for super-strong spider silk.

MIT Technology Review, August 4, 2010, by Katherine Bourzac  –  Researchers have been trying to make artificial spider silk–a lightweight, tougher-than-steel material that could have countless industrial applications–for decades. In an important step toward that goal, researchers at Tufts University have created genetically engineered microbes that produce more of the proteins needed to make spider silk than ever before.

Dragline silk–the type spiders use for the rims and spokes of their webs–is tougher and far lighter than steel. Engineered bacteria can produce the proteins needed to synthesize this silk, which is spun together to make fibers. However, previous efforts to make spider silk using bacteria have been hamstrung for several reasons. First, researchers have had an incomplete picture of the dragline silk gene sequence. And second, they’ve had limited success in modifying the bacteria to produce enough of the proteins.

David Kaplan, chair of the biomedical engineering department at Tufts University, has pioneered the application of silkworm silk in medical devices, biodegradable electronics, optical devices, and adhesives. He believes that spider silk, which is stronger than the silkworm variety, could open up new applications, but says, “It hasn’t been explored as much because we haven’t had enough material.” Spiders are aggressive and territorial and thus can’t be farmed like silkworms.

Bioengineers have had only modest success in getting microbes to make spider-silk proteins. Chemical giant DuPont tried unsuccessfully to develop a bacteria-produced silk product in the 1990s. Part of the problem is that spider silk is made from a very large protein with a highly repetitive genetic sequence, making it hard to decode, says Christopher Voigt, professor of pharmaceutical chemistry at the University of California, San Francisco.

Last year, researchers using new sequencing technologies produced the first complete genetic sequence for spider silk. Before that, researchers were forced to use truncated silk genes, and fibers made using these genes were not as strong and tough as natural silk.

Even with the full dragline silk gene sequence, producing artificial silk is a challenge. Making enough of the protein requires a larger amount of starting material than the bacteria naturally contain. Working with researchers at the Korea Advanced Institute of Science and Technology in Daejeon and Seoul National University, Kaplan added the full silk gene to E. coli and then altered the bacteria’s protein-making pathway so that it makes sufficient quantities of the amino acids needed to enable silk production. Previously, engineered bacteria have only been able to produce tens of milligrams of the protein per liter. Kaplan’s E. coli yield one to two grams per liter.

“They’ve clearly shown that E. coli can make these large proteins, and engineered them to have the resources to do it,” says Randy Lewis, professor of molecular biology at the University of Wyoming. Lewis predicts that it will be possible to use a bacterial system to produce kilogram quantities of artificial spider silk within a few years.

Kaplan says that’s his plan. “We’d like to turn it into a continuous production process,” he says.

Kaplan says what’s needed now are more energy-efficient methods for making the proteins into fibers. Using spinning methods similar to those used to make polymer fibers such as polyester, his group has created fibers from the team’s proteins with properties comparable to natural dragline silk in terms of strength, elasticity, and toughness. However, because spider-silk proteins are finicky and insoluble in water, spinning them into fibers requires high-temperature processing and harsh solvents.

The fibers “take a huge amount of energy to put together,” says Kaplan. Materials scientists would like to make silk fibers the way spiders do: at ambient temperatures, with no harsh solvents.

A novel approach to the problem is being pursued by Luke Lee, director of the molecular nanotechnology center at the University of California, Berkeley. He is designing spinning systems that incorporate microfluidic channels designed to provide the salt- and solvent- gradients found in spider glands. A company called Refactored Materials, founded by students of Lee’s and Voigt’s, is also working on the spinning problem.