The Bionic Frontier
Katie Lee Anderson doesn’t say much on the July 2003, day when she arrives at St. Vincent Medical Center in downtown Los Angeles. Kirk and Laura Lee Anderson, parents of the slender, blond 19-year-old from Orem, Utah, do most of the talking. But Katie is definitely the focus of conversation, because later that day--if all goes well--she will make medical history. An array of electrodes will be inserted into the base of her brain, and she will become a living, breathing bionic woman.
Katie’s hearing problem became apparent five years earlier, when she was 14. “She was no longer racing her siblings to answer the telephone,” says her father. “When we asked her why, she said she couldn’t hear on the phone.” An MRI scan revealed the cause: noncancerous tumors were compressing the nerves that connected her inner ears to her brain. Her condition, called neurofibromatosis type 2, is genetic, but Katie is the only member of her large family to have it. Her hearing continued to deteriorate despite two operations. By the time she arrives in Los Angeles, she can’t even hear claps of thunder. She speaks quite normally, but she can’t follow the conversation well enough to join in.
Still, Katie opened up in a series of e-mails about the toll that deafness had taken on her life. “I wasn’t a popular kid at school,” she wrote, “and at some point I felt that I was a ghost because I didn’t have a lot of friends. I would just sit there and be quiet...I couldn’t really hear the teachers.” After graduating, she worked for a while as a teacher’s aide but eventually was laid off. Her co-workers were “complaining that I couldn’t answer the phone and that it was a burden on them. I feel somewhat isolated from my friends’ lives--because I’m hardly ever invited to do stuff with anyone.”
Because Katie’s auditory nerves no longer function, hearing aids or even cochlear implants can’t help. Her world has grown excruciatingly small. So when her parents heard about a startling option in Los Angeles that hinted at the emerging science of “neuroprosthetics”--the use of electronic devices to substitute for damaged neural tissue--they began asking questions. The Andersons eventually brought their daughter here for a revolutionary treatment--one that offers a glimpse into what may be possible for those, like Katie, who have been betrayed by their bodies and can’t wait for the nascent promise of brain or spinal-cord regeneration.
Since becoming a quadriplegic in 1995, actor-director Christopher Reeve has dedicated himself to the quest for spinal cord regeneration, the Holy Grail of neurology. The bulk of the money generated by the Christopher Reeve Paralysis Foundation has promoted research into biologically based therapies, such as stem-cell research that could regenerate damaged brain cells and possibly restore lost functions to patients such as Katie.
Given that, the decision to implant an electronic device into Katie’s brain may come across as Rube Goldbergian, inadequate or unnecessary. Yet the biological therapies have been much slower to develop than researchers had hoped five years ago. Stem cells have proven tricky to control, and early clinical tests of gene therapy have caused at least one death and two cases of leukemia.
Neuroscientist Terry Hambrecht, a longtime researcher at the National Institutes of Health, understands why Katie and those like her pursue potential solutions now rather than wait for the next wave of scientific progress. “Regeneration, stem cells--they have tremendous promise, but I’m very skeptical that they are going to do anything useful in our lifetime,” Hambrecht says. “Neuroprosthetics not only promises, but has delivered.” Ross Nathan, a Long Beach-based hand surgeon who has implanted neuroprosthetic devices, echoes the point. “It’s hard to get up there and criticize Reeve,” he says. “You feel bad for him, and he does have good intentions. But his efforts are not improving anyone’s quality of life, I believe.”
Although Katie’s operation was to be a world’s first, scientists have been developing the field of neuroprosthetics for many years. Hambrecht, who started the NIH’s neuroprosthetics program in 1972 and ran it until 1999, recalls an account of an experiment performed around 1800 by electricity pioneer Alessandro Volta. The ever-curious Italian put wires in each of his ear canals and connected them to his newly invented battery, which put out about 60 volts. “I received a shock in the head,” wrote Volta, “and a few moments later, I began to be conscious of a sound, or rather a noise, in my ears that I cannot define clearly. Because of the disagreeable, and I feared dangerous, sensation of the jolt in the brain, I did not repeat the experiment.” What Katie’s doctors planned to do to her was, in principle, what Volta did to himself, but refined by two centuries of advances in neuroscience and electrical engineering.
Probably the best-developed application of brain-stimulation technology is in the treatment of Parkinson’s disease and other disorders of movement. For many years, the only treatment for involuntary movements that did not respond to drugs was to surgically interrupt the brain circuits that generate them. These operations, with names such as thalamotomy and pallidotomy, occasionally had devastating complications, such as affecting the patient’s ability to speak.
In the late 1980s, neurosurgeon Alim-Louis Benabid of the Joseph Fourier University in Grenoble, France, tried implanting an electronic stimulator in the brains of patients with Parkinson’s disease. He found that activation of the device subdued the patients’ tremor just as effectively as the standard surgery, without the destruction of any brain tissue. Benabid’s device has become a commercially successful product manufactured by the Minnesota-based Medtronic Inc. and is now used routinely around the world. Refinements in the placement of the stimulators have made it possible for the device to relieve other symptoms commonly experienced by Parkinson’s patients, such as their halting gait.
The electronic wonder that was to be implanted in Katie’s brain makes the Medtronic stimulator seem as high-tech as a bowling ball.
Katie isn’t a particularly outgoing young woman, and this morning, waiting for the anesthetist to arrive, she seems caught between her fears about brain surgery and unwanted publicity and her hope that her hearing might someday return to normal. Her e-mails are more explicit. “I am a little scared because I am not really a person who goes first or who likes to do stuff in front of a crowd,” she writes. “I hope the implant will make it so I can hear sound. I hope it will help me with my education and other things I want to do in life. I am happy and proud too, because I am doing something that can make a difference in people’s lives.”
Less ambitious versions of the device destined for Katie’s brain have been around since 1979. Researchers at the House Ear Institute, located across the street from St. Vincent Medical Center, introduced an “auditory brainstem implant” that year that could be placed on the surface of the brainstem, near where the auditory nerves enter it. That device has since been implanted in more than 400 people, and it offers a rudimentary form of hearing that can be useful as an adjunct to lip-reading. It also can alert the person to environmental sounds such as a knock on the door. It doesn’t usually allow for real speech comprehension though. That’s because the human auditory system works by breaking sounds down into their constituent frequencies (or pitches) and transmitting these frequencies through different neural pathways for analysis. A stimulating device placed on the surface of the brain does a poor job of stimulating specific pathways; it tends to stimulate them in non-specific ways, generating noises that inhibit speech perception.
But for the past several years, a team at the House Ear Institute and the Huntington Medical Research Institutes in Pasadena has worked on the new implant designed to address this shortcoming. The main innovation in the new device is a set of eight tiny, needle-like electrodes, mounted on a button about three millimeters across. When inserted directly into the auditory center in the brainstem and connected to a microphone and a frequency-analyzing microprocessor, the electrodes are designed to provide independent stimulation of several different frequency pathways. If it works, the user should be able to detect the rising and falling tones that are the building blocks of speech.
That was the theory, at least, and the theory was supported by some limited testing of the device on laboratory animals. But because the electrodes in the new device were designed to enter the brain rather than lie on its surface, their exact placement was crucial. Unfortunately, the anatomical layout of the auditory centers is not as well understood in humans as it is in animals. The only way to test the new device was to go ahead and implant it in a human volunteer.
Katie looks more like a vulnerable child than an adult as she lies unconscious on the operating table, her long hair shorn away in a wide swath behind her right ear. Derald Brackmann, an otologist who specializes in surgery of the inner ear and auditory nerves, begins with an incision into Katie’s scalp. A group of House Ear Institute researchers who have been involved in the project watches the proceedings by closed-circuit television. The team’s co-leader, auditory neuroscientist Bob Shannon, gives a running commentary.
To expose Katie’s brainstem, Brackmann drills through her right temporal bone, an extremely dense part of the skull that reaches from behind the ear almost to the center of the head. This through-the-bone route carries less risk of neurological complications than the traditional route, which involves exposing and raising the back of the brain. The main risk associated with Brackmann’s approach is hemorrhage, and in fact the operative site does bleed alarmingly on several occasions. Each time, however, Brackmann stems the flow with electrocautery and by packing the hole with coagulant foam.
After four hours of painstaking work, Brackmann reaches Katie’s brainstem, the region of the brain where it narrows to connect with the spinal cord. At this point he hands over the operation to neurosurgeon William Hitselberger, who spends another hour removing every trace of the tumor that caused Katie’s deafness. His aim is not to restore Katie’s natural hearing--the damage to her auditory nerves cannot be reversed--but to prevent the tumor from encroaching on the vital nerve centers in her brainstem such as those that control breathing. Then, to supplement the new device Katie will receive, Hitselberger places the old-style auditory implant so that its 14 electrical contact points are lying against the surface of Katie’s brainstem.
Finally, the moment arrives to install the new device. To do its job properly, the array of needle-like electrodes must be driven into the brain tissue at the exact spot where the underlying auditory centers are located. Hitselberger loads the device into a gadget that works like a miniature staple gun. He roams over the exposed brain with the tip of the gadget, trying to locate the slight bulges and folds in the terrain that identify the position of the auditory centers. The movements of Hitselberger’s instrument, viewed through an operating microscope and displayed on a cinema-sized screen, seem unbearably coarse and uncertain. In reality, they only range over a few millimeters. Doug McCreery, the neurophysiologist who designed both the electrode array and the insertion tool and who performed the animal testing, is in the operating room. As he discusses the exact placement of the array with Hitselberger, his voice betrays some anxiety, and with good reason: Ten years of his research are soon to be validated, or not.
Finally, the team agrees on the optimal location. Hitselberger pushes a button, and the electrode array shoots into the brain in the blink of an eye. There’s no turning back now. All that remains is to arrange a rat’s nest of electrical leads within the deep hole Brackmann has created, pack the hole with Katie’s own fatty tissue (obtained from a mini-liposuction in her abdomen), cover it with titanium mesh to replace the missing bone and sew her up. After a night in the intensive-care unit, Katie returns to Utah with her parents. She is to spend six weeks recuperating at home, then she’ll return to Los Angeles in September so that the device can be switched on and tested. Only then will Katie know if it works.
By opting for a neuroprosthetic solution, Katie joined a remarkable collection of bionic medical pioneers, many of whom live in Southern California. Lois Aguilar is a 57-year-old Japanese American woman who worked in the purchasing department of a large store but was left a quadriplegic after breaking her neck in a 1996 car accident. She now lives with one of her sons in a spacious home in Rancho Cucamonga whose open layout allows her to maneuver her bulky power chair around the house.
Aguilar uses an implant called a Freehand that was developed by a team led by biomedical engineer P. Hunter Peckham of Case Western Reserve University in Cleveland, Ohio. The Freehand doesn’t reconnect Aguilar’s severed spinal cord--such a feat is still impossible. Rather, it senses the voluntary movements that Aguilar can still generate in her right shoulder and converts these movements into electronic command signals sent via implanted wires to stimulating electrodes in the muscles controlling her left hand.
When Aguilar’s implanted device was first tested, she couldn’t believe what was happening. “I moved my shoulder and my hand was doing this”--she made a grasping motion--”and I said ‘Oh my God! It’s actually moving!’ ” Controlling the Freehand has since become second nature to her. She uses it for everything from brushing her teeth to feeding herself, from changing channels on the TV to turning the pages of books. “It’s improved the quality of my life tremendously,” she says.
The movements provided by the Freehand--a simple pinching motion, as for holding a key or a pencil, and a grasping motion for holding larger objects such as cups--are far short of what an able-bodied person’s hand can perform. But as Ross Nathan, the surgeon who installed Aguilar’s implants, noted, “For someone who has nothing, a little is a lot.” The same can be said of those who are totally blind but may benefit from ongoing research into a “retinal prosthesis” by USC ophthalmologist Mark Humayun in collaboration with the Sylmar-based Second Sight Corp.
There are, of course, plenty of researchers who remain committed to Reeve’s vision--the development of biological therapies based on stem cells, growth factors, genetic engineering and the like. Neuroscientist Evan Snyder, for example, who recently left Harvard Medical School to direct the developmental and regenerative cell biology program at the Burnham Institute in La Jolla, has isolated neural stem cells from human fetuses. He now can grow unlimited quantities of these cells in the lab.
Snyder believes that transplants of neural stem cells--cells that have the capacity to replace any kind of cell in the brain or spinal cord--eventually will be the method of choice for treating a wide variety of neurological problems, ranging from injuries and strokes to brain cancer and inherited diseases. Stem-cell therapies, says Snyder, have the potential to restore the normal function of the nervous system better than any engineering solution. Even Katie’s deafness may respond to biological therapies, if the means can be found to persuade her severed auditory nerves to regrow.
Snyder even sees a place for neuroprosthetics in a future where damaged brain cells can be regenerated. “It shouldn’t be an either/or,” he says. “It’s probably going to end up being a combination, intelligently orchestrating the virtues of both approaches.” Snyder says he is working on a project to see whether electrical impulses, such as might be generated by a prosthetic device, can help mold what the stem cells do, where they go and what connections they make. “So the two approaches may interface with each other.”
When Katie returns to Los Angeles in early September, a dozen doctors and researchers crowd into audiologist Steve Otto’s tiny lab at the House Ear Institute to watch the implants be switched on and tested. First, Otto attaches a small radio transmitter to Katie’s scalp and prepares to send electronic pulses to the various electrodes now inside her head. Katie remains expressionless and seemingly unexcited, but that’s because the nerves that control her facial muscles also were damaged by her tumors. Even a smile is difficult for her. “I’m a little scared,” she wrote in an e-mail a few days earlier. “I hope that I will get to hear some type of sound even though I don’t know what it will be like. I’m hoping that it will help me step out of my box and get a job and have a social life.”
Otto begins by testing the old-style brain-surface device. He activates one of its electrical contact points with a very low current. Katie says nothing. Then Otto gradually raises the current level, and as he does so he slowly raises his hand in the air to show Katie how the stimulus is increasing. His hand is about halfway up from the table when Katie says, “I feel a tingle in my face.” Apparently that particular contact is not located near enough to the auditory center but is instead stimulating nerve cells that carry sensory information from the face. Katie’s parents look disconcerted, no doubt wondering if the whole procedure has failed.
Otto remains calm. He switches off the stimulation and activates a different contact point. This time, when Otto raises his hand to a medium height, Katie suddenly says, “I hear a ding.” A collective sigh of relief goes around the room. Whatever else happens, Katie is going to get some kind of hearing out of the implant. When Otto finishes the tests, he concludes that 12 of 14 contact points are capable of providing the sensation of sound. It’s a good start.
Now Otto turns his attention to the new, penetrating-electrode array--Katie’s best hope to again understand human speech. Here the results aren’t as good: Only one of the eight penetrating electrodes provides a sound sensation; others produce a sensation of tingling in Katie’s hand or have no effect at all. Apparently, in spite of the surgeons’ best efforts, the penetrating array has not been implanted in precisely the right spot in Katie’s brain. With only one electrode connecting, the penetrating array is not likely to provide Katie with the ability to understand speech. No one says as much, but the disappointment is palpable.
Detailed testing continues for several days, but the goal of speech comprehension remains elusive. Her performance is roughly similar to that of people who receive the standard surface implant.
Seven months later, Katie says she is grateful for even the limited ability she now has. “I use the implant every day,” she writes. “I am lip-reading better and hearing better. I was playing hide-and-seek with one of my nieces and she was hiding in the closet. I knew she was somewhere close by but I didn’t know where till I could hear her giggling and I found her. I can be watching TV down in our basement and if my dad calls sometimes I hear it and respond to him.”
She has no regrets about being a medical pioneer. “I always wanted to make a difference in the world, even if the result is not like what I thought it would be. I am grateful for it and happy it has helped me so much.”
There is a postscript: Molly Brown followed Katie down the pioneer’s path, in November of last year, allowing the same research team to implant a similar electrode array. Like Katie, the 43-year-old mother of three from Lynden, Wash., became deaf as a consequence of neurofibromatosis type 2. Besides wanting to regain her own hearing, Brown was especially motivated to volunteer for the procedure on account of her children. Though they’re currently healthy, her children are at risk of developing the same hereditary condition. “My No. 1 reason is to give them hope,” she says. “It’s very lonely to be deaf, especially if you didn’t grow up that way.”
Brown knew that Katie’s implant hadn’t worked as well as had been hoped. “I felt badly for her,” she says, “but I was undaunted. I was maybe even more determined to go through with it.”
Based on their experience with Katie, the researchers made some changes in the procedure, especially in the placement of the penetrating electrodes. The changes paid off. When Brown, accompanied by her husband Allen, returned for initial testing in mid-January, the audiologists found that seven of the eight penetrating electrodes produced sound sensations. What’s more, the individual electrodes were generating sounds of different pitches, just as they had hoped.
Within 24 hours, Brown was able to distinguish some words by hearing alone. Her comprehension of speech and her recognition of environmental sounds has improved since then. “I’m thrilled,” she writes. “I’m just astounded at the technology! I was shown some X-rays of my brain with all the electrodes in there . . . wow, it was just amazing . . . all those wires! I feel much more connected to the world.”
But the most telling moment occurred on the day of her initial testing. Her 18-year-old son Michael telephoned Allen to see how Molly was doing, and Allen handed his wife the phone. “I love you,” said Michael. Without hesitation, Molly replied: “I love you too.”