U.S. Army sergeant Michael Sanchez was on patrol in Samara, Iraq, one night in August when his unit noticed what seemed to be garbage in the middle of the road. It was actually a bomb. "It was kind of like in the movies," he says. "There's a little white flash and then you open your eyes and you're lying on the ground. It's so painful you can't even breathe."
Sanchez was so badly wounded that doctors in Iraq were forced to amputate his right leg below the knee. Back in the United States, some surgeons thought they should remove his left leg as well. Now, after twenty-four operations, Sanchez is walking again with the help of a lightweight artificial limb while he undergoes a frustratingly long and grueling procedure to save his left leg.
More than 1,500 U.S. troops have died fighting the war in Iraq. Although this number is well known - the New York Times, for example, updates it prominently whenever a U.S. combatant is killed - what's less frequently reported is that the number could easily be much higher. In a development that has major implications for soldiers like Sanchez, as well as for the medical system that takes care of them, U.S. troops in Iraq are surviving their wounds at unprecedented rates. Less than 10 percent of Americans wounded in action in the war on terror have died, according to U.S. Department of Defense figures, compared to 24 percent in Vietnam and 30 percent during World War II.
Some of the credit for the lower fatality rate goes to improved medical care, both on the battlefield and in military hospitals, as well as to more effective body armor, which has reduced the number of life-threatening injuries to vital organs. The nature of war wounds has changed, too. In earlier conflicts, most amputation injuries were inflicted by conventional weapons: shrapnel or bullet fragments. The main weapons of Iraqi insurgents, by contrast, are roadside bombs and rocket-propelled grenades, which are intended to maim as well as kill. Those weapons have caused greater numbers of nonlethal wounds, injuring more than one limb at a time and causing higher rates of such disabilities as blindness, deafness, and brain damage. The nature of the war has also taken a psychological toll; with no safe zone, every soldier is effectively on the front line. Further complicating matters, about 40 percent of the troops in Iraq are members of the National Guard or Reserves. They are unaccustomed to war zones like Iraq, and when they return home, they must immediately pick up the lives - jobs, soccer practices, mortgages - they left behind.
All of which has left the U.S. Veterans Administration (VA) scrambling. It has recently stepped up research into new and better treatments, from easier-to-use artificial limbs to ways of preventing and treating post-traumatic stress. At Brown, researchers are undertaking a number of loosely related projects aimed at helping soldiers cope with the physical and emotional demands of their drastically altered lives. Some of the projects are focused on post-traumatic stress and other readjustment issues (see "The Wounds No One Can See," page 36). Perhaps most remarkable, though, is the newly established Center for Restorative and Regenerative Medicine, an interdisciplinary effort to create a "biohybrid" artificial limb made partially of the patient's own skin and bone and controlled in part by his or her thoughts.
The VA has allocated $7 million for the center, which is headed by Professor of Orthopedics Roy Aaron, to conduct research at Brown and MIT. Another $6 million will open a research and treatment facility at the Providence VA Medical Center. Research includes work by Brown neuroscientists to fine-tune a system that uses a brain implant to pick up movement commands, and an attempt by robotics experts to develop artificial knees and ankles that perform more like the real thing. Metals engineers, meanwhile, are joining forces with biologists to grow human skin on titanium, in an effort to better attach artificial limbs to the body. And specialists in growing bone and cartilage are applying their expertise. In addition, the team will use virtual reality to test, for example, whether a marine with a prosthetic leg could serve on a ship with a wet or rolling deck.
U.S. Army major H. Michael Frisch '90, the trauma surgeon in the orthopedic surgery department at Walter Reed Army Medical Center in Washington, D.C., and the doctor who saved Sanchez's left leg, is among those eagerly awaiting results from all this research. A Brown neuroscience concentrator, he joined the military to pay for medical school at Georgetown University and now performs amputations, follow-up operations, and limb-salvage procedures on soldiers like Sanchez - soldiers who usually want to know: Will I walk again? Will I have the strength to play with my kids? Can I still be an infantryman?
"They're worried about their future and what they'll be able to do," Frisch says. "Their families are adjusting. They may get more bad news about their buddies back in Iraq. Any setback can bring them really down." Frisch hopes that someday Aaron's team will help give his patients a brighter future.
Aaron and his group aim to bring the latest technological and biological breakthroughs to bear on problems that have remained intractable for decades. For example, one of the major obstacles to fitting an amputee with a prosthetic arm or leg has always been the length of the remaining bone. When a soldier loses a leg just below the hip or knee, or an arm just below the shoulder or elbow, there is not enough residual limb to stably attach a prosthetic. "It's frustrating," Frisch says, explaining that, without enough to grab onto, an artificial limb may not fit or function properly. Because an artificial leg tends to rock and bend when connected directly to the knee, surgeons sometimes amputate the knee just to attach a device to a patient's thigh more sturdily. But at the mere mention of such a step, soldiers have refused to talk to Frisch for days. And a major drawback of an above-the-knee prosthetic is that walking on it requires a staggering amount of energy.
What patients really need, the Brown scientists believe, is a longer residual limb. With several inches of limb below the knee, the soldier would expend no more energy to walk than an able-bodied person would. Likewise, when attached directly to the shoulder, an artificial arm can be so inefficient that a patient often stops using it. But with a few extra inches of upper arm a patient can propel that residual limb forward to open a prosthetic hand.
Michael Ehrlich, chairman of the Brown Medical School's orthopedics department, has been lengthening bone for thirty years, primarily on patients with congenital disorders. In the mid-1980s, while chief of pediatric orthopedics at the Massachusetts General Hospital, he became one of the first surgeons in New England to lengthen bones using what is called the Ilizarov method. The technique involves breaking bone, wiring its fragments apart, and then allowing new bone to grow in and re-fuse them. "If you cut out part of the liver, it doesn't regrow," Ehrlich explains. "If you cut out part of the stomach, it doesn't regrow. But if you cut bone in the right way, it regrows and looks as good as new."
The Ilizarov method is normally used to treat such conditions as congenital bone malformations and fractures that don't heal correctly. Frisch used the Ilizarov method to help rebuild Sanchez's damaged left leg. Now Ehrlich wants to apply the same technique to residual limbs that are too short for prosthetics. Aaron hopes that by the end of December, Ehrlich will be performing the Ilizarov surgery on amputees from the Iraq war. They will most likely travel to Providence for surgery, stay at Walter Reed or Bethesda (Maryland) Naval Hospital while the bone regrows, and then return to Providence for the rest of the procedure. In addition to his work in the operating room, Ehrlich will conduct basic research on rats to lengthen bone more quickly and to make the new bone stronger. "The bones don't always fill in," he explains, "or they fill in very slowly, or they angle, or after they heal they break."
While Ehrlich is working on bone repairs, Deborah Ciombor '79, an assistant professor of orthopedics and associate director of the Center for Restorative and Regenerative Medicine, will focus on growing new cartilage. The standard technique, as she describes it, is to remove cartilage cells from a joint, allow them to replicate in the lab, and then insert them back inside the body. For the first year or so, the surgery can seem like a success. "But the repair doesn't hold," Ciombor says. "No one's been successful at it." Her approach is slightly different and builds on research she has been conducting since graduate school: she will try to mimic the way cartilage is formed in embryos. Ciombor expects to begin animal testing sometime in 2006. If she's successful, human testing will follow. "We're hoping to get to a point," she says, "where we can say to the surgeons, ?Take the traumatized tissue, but don't make a judgment as to how short the residual limb is going to be. Give us a shot at it.' "
One problem, however, is that it takes at least five months for Ehrlich to add two inches of length to a bone. In February, he, Aaron, and Ciombor visited Walter Reed, where they met another one of Frisch's patients, a soldier who'd lost one leg near the hip and the other above the knee, and who also had serious injuries to both arms. The solder's wife and child, who were visiting at the hospital, were eager to have him home, which, Ehrlich says, raises an important question: "If we're going to intervene in the process and delay him from going home, are we helping him? We know medically we're helping him. But we know you have to think beyond the medicine. You have to think about the patient."
Sanchez has spent eight months waiting for the bone in his left leg to regenerate and grow stronger. He wants to get home to San Diego, buy a house with his wife, and start a family. He thinks about going back to school and coaching high school sports.
Aaron worries about raising hopes among such soldiers. "I'm amazed on the one hand at the level of bravery and optimism," he says. "[But] I don't want to go down there and pretend I have some magic dust I can sprinkle on these guys."
During the Vietnam War the standard-issue prosthetic was made of peach-colored plastic. "It was fashioned to look like a real leg," says Stephan Fihn, acting chief research and development officer at the VA, "but it didn't function anything like one. It was stiff, inflexible, poorly resilient." Today's artificial legs are made of lightweight titanium and enable an amputee to run and ski. Springs absorb shock and tension. Built-in computer chips adjust over time to a user's gait and respond to changes in momentum. So advanced is the technology that one captain who lost his foot has returned to combat.
But even these limbs have drawbacks. Like the older models, today's prosthetics attach to the body with a cuff that fits around the residual limb. The patient's skin bears the brunt of the load, a design that can be not only chafing but also inefficient. Scientists hope to render the cuff obsolete. Clyde Briant, Brown's dean of engineering, has teamed up with Jeffrey Morgan, an associate professor of medical science, to improve a technique called osseointegration. Developed in Sweden, osseointegration is a means of attaching a prosthetic directly to the bone. Doctors drill a hole in the bone and insert a small piece of titanium. The titanium connects to another piece of metal that protrudes from the skin and attaches to the prosthetic. "This puts the load right on the bone," Morgan says, "where it should be."
The problem is that skin, sensing that the protruding metal is a foreign object, refuses to close up. "It's not a good seal," Morgan explains. "There's a high risk of infection." Sometimes the skin actually grows around the metal in an effort "to take it out like a big splinter," he adds.
Morgan grows human skin in his lab. Before arriving at Brown three years ago he worked at Harvard Medical School and at the Shriner's Hospital for Children, a burn center in Boston. "Skin," he notes, "is more complex than some of the materials used to build skyscrapers." Working with two bioengineering graduate students, Brian Holt and John Jarrell '88, Morgan and Briant will try to create a better seal around the metal. Briant, a titanium expert, will experiment with a common alloy used in aircraft engines, roughening its surface to try to make the skin adhere better. He will also test different metal compositions.
"It's a whole new area for me," says Briant, who worked for eighteen years at General Electric. "In engineering," he says, "you try to always help society, but it might be through cars or, at GE, a better lightbulb. This is very direct. This is my first real foray into putting metals into a person."
"For me," says Fihn, "the holy grail for decades has been a limb that is not only strong and functional but can perform as well, or maybe better, than the native limb."
Today's amputees present a new challenge for the VA, which for decades has treated primarily elderly veterans facing amputation as a result of chronic health problems such as diabetes. The VA fitted 6,000 prosthetics in 2004, Fihn says, at a cost of $51 million, and repaired another 40,000. Today's war amputees, by contrast, are young and eager to resume activities like marathon running and mountain climbing. Many want to return to their units. Frisch remembers one soldier who, three days out of battle, arrived at Walter Reed with one leg amputated below the knee and the other above the knee. Before Frisch could even introduce himself, the soldier asked, "When do I get my legs?" Once, Frisch treated a sergeant whose only concern was finishing his amputation surgery quickly so he could fly to Germany to greet his unit when it arrived from Iraq.
Unfortunately, though, even the best prosthetics cannot replicate natural movement. "You can't point your toe," Sanchez says. "You can't bend your knee past ninety degrees. Walking uphill is a problem because the ankle doesn't give." Neither can the new prosthetics interact with the brain and nerve signals that command the body to move. As part of the biohybrid limb initiative, Hugh Hare, director of the biomechatronics group in the MIT Media Laboratory, is working to develop robotic knees and ankles that are powered by artificial muscles, enabling a user to walk and climb more easily and naturally. To control the new joints, Herr will use a wireless microchip injected into existing leg muscle. The chip, called a BION and developed by the Alfred E. Mann Foundation, is designed to pick up the nerve signals that would normally command a real knee or ankle to move.
John Donoghue '79 PhD, chairman of the neuroscience department, is conducting similar research. He has developed a brain-implantable system to pick up and translate the signals in the brain that command the body to move. He is currently testing the device in two quadriplegics. The first patient is able to open and close a robotic hand with his thoughts (see "Thinking the World into Motion," January/February). Donoghue hopes eventually to apply the system to amputees.
To determine how the treatments are working, Linda Resnik and Vincent Mor of the Medical School's community health department will evaluate existing patient surveys and physical tests that measure an amputee's mobility, satisfaction, and quality of life. They will study several hundred amputees in an effort to help the team choose outcome measures for the center's human trials.
While similar work is under way at other labs around the country, Roy Aaron says Brown is the only place taking a comprehensive approach. Tissue engineering, for example, is a popular area of study, but Brown is the only institution integrating it with research in robotics, neuroscience, and engineering, as well as in mental health, all in an effort to help amputees.
Aaron expects the work to benefit other patients, too. The Briant-Morgan collaboration could have applications for catheters, pacemakers, and other artificial materials that interact with the body. The bone-lengthening research may help doctors better treat osteoporosis or broken bones.
While the VA has been funding amputee research for decades, it has not been a popular area of study. "It hasn't been the public health problem that heart disease and cancer and bioterrorism have been," Aaron explains. The Brown researchers, however, believe science owes a debt to wounded troops. "This is an all-volunteer army," Ehrlich says. "They've given up part of their being to help protect us." When they come home, science can, in some small way, return the favor.
Emily Gold Boutilier is the BAM's senior writer.
