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Turning Thoughts Into Actions
It's Super Bowl Sunday, and it's game time. You want to turn on the TV and get to the right channel ASAP. So a small area of your brain called the motor cortex processes and sends intricate electrical signals to your arm and hand, which allow you to pick up the remote control and operate it in time to see the kickoff. But if you don't have the use of your arms, like the hundreds of thousands of people in this country who are paralyzed or have nerve or muscular damage, you have to wait for a caregiver to do it. That is, until this past year.
In June a young man who is completely paralyzed underwent surgery to implant a small sensor in his brain that allows him to write e-mail, play video games, change the channels on his TV and open the curtains -- using only his thoughts.
Although FDA approval is still several years away, this is the beginning of "a new age of neurotechnology," says John P. Donoghue, Ph.D., chair of the department of neuroscience at Brown University. For 20 years he and his lab colleagues studied monkeys to learn how we go from thought to action. Eventually they decoded how that works, and then Richard Normann, professor of bioengineering at the University of Utah, invented a sensor that detects neural activity in the brain. This led to development of the BrainGate Neural Interface System, to be used in a human clinical trial.
RD: How difficult is this surgery?
Donoghue: The surgeon makes a craniotomy that's the diameter of a 50-cent piece. The sensor, which is the size of a baby aspirin with 100 tiny hair-like appendages, is implanted in the region that issues commands to the arms. The software tells the surgeon exactly where to go and the whole surgical procedure takes about two and a half hours. Afterward only a penny-sized connector to the computer can be seen from the outside.
How does the system work?
The patient directs his thoughts to move the cursor on his computer screen. The sensor in his brain picks up those hard-to-detect electrical signals and sends them through three computers that process them into signals just like those from a computer mouse. These processors, which currently sit on a cart and are not mobile, will eventually become wireless and small enough to fit inside the body.
So when he's connected, the patient can just "think" the cursor from place to place on-screen like the rest of us use a mouse. What else can he do?
He can also connect to other devices through the computer, such as a TV set, the control that opens and closes the curtains, a powered wheelchair or even a mechanical hand. Eventually we could hook this up to the person's actual hand.
Could the implant allow him to, say, play the piano?
No, not yet. And not unless he could play it before! The simple opening and closing of the hand is not that hard to do. But to pick up a coffee cup and drink from it -- that's a challenge.
Could the implant allow him to walk?
Walking is extraordinarily tough. Not only do you have to move the legs, but you have to balance. And the system doesn't deal with the balance problem at all. That's why we're focused on the arm, because it's simpler, and it allows you to interact with the world. If you want to understand a bit of what it's like to be paralyzed, try sitting on your hands for three hours. You can't do anything.
What if a stem-cell breakthrough allowed us to regenerate nerve function in spinal-cord-injury patients? Would that make the BrainGate obsolete?
I hope that happens! But if stem cells are able to regenerate the spinal cord, something will have to give instruction to those growing nerve fibers on how to hook up. So maybe we can use the device to help instruct the nervous system in how to use the stem cells in a more effective way. Or maybe we place stem cells in the implant that will be driven out at the right time to help reconstitute the circuits that have been damaged.
Could this technology be used to create superhero-type enhanced humans, or super-villains?
Technology in and of itself is neither good nor bad; it's how we apply it. Augmentation of function? Creating super-memory and super-motor abilities? Yes, I'm sure you could come up with all kinds of applications that many people would be uncomfortable with. We should be discussing the ethical implications of these types of devices. But that can't stop us; this technology may profoundly help people with disabilities.
New Hope for Cancer Patients
Think of it as a switch to turn off tumor growth. The new drug Avastin combats colon cancer in a revolutionary way: by shutting down its blood supply. Starved of oxygen and crucial nutrients, malignant growths shrivel -- slowing the spread of the disease, which currently kills about 57,000 Americans a year. As an added punch, the drug, the first of its kind to win FDA approval (in February 2004), also helps increase the effectiveness of standard chemotherapy.
While Avastin isn't a cure, it's extending the lives of the sickest patients. "The battle isn't won yet," says Leonard Saltz, M.D., colorectal disease management team leader at Memorial Sloan-Kettering Cancer Center in New York City, "but I'm excited to have a new weapon against this deadly disease."
For decades, doctors have known that cancer needs to form a network of new blood vessels to grow and spread. In 1989 Napoleone Ferrara, M.D., discovered the protein that fuels this process, which he called VEGF (vascular endothelial growth factor). "We spent years developing an antibody to block VEGF in mice, and the results exceeded our greatest expectations, because it was active against virtually every type of tumor," reports Ferrara, a fellow at Genentech, Inc., in South San Francisco.
Will Avastin, the human version of this antibody, have the same effect in people? The therapy is currently being tested for cancers of the lung, kidney, breast, ovary and pancreas, with promising preliminary findings. But Ferrara adds that its potential may be even broader. "We're in phase III trials of an Avastin derivative to treat age-related macular degeneration, a major cause of blindness. And it's possible that it might work for rheumatoid arthritis and gynecological diseases such as endometriosis," he says, which also stem from excessive blood-vessel growth.
Other exciting news in the war on cancer: the first proof that inflammation also plays a key role in tumor growth. For example, chronic heartburn can lead to esophageal cancer. "It's the dark side of the immune system's ability to fight infections," explains Michael Karin, Ph.D., professor of pharmacology at the University of California, San Diego. A September 2004 study by Karin and other researchers showed that in mice with breast or colon cancer, inflammation triggered the release of two immune system chemicals that helped tumors spread. But the good news is that the animals also produced a natural protein that kills cancer cells. However, the helpful compound wasn't as potent as the harmful ones, so the researchers manipulated the chemical balance to boost its effects.
The result? "The outcome was reversed, so the mice's survival was significantly increased," says Karin, who speculates that this finding will someday lead to ways to strengthen our natural defenses against cancer, or drugs to block the damaging effects of inflammation before cancer sets in.
Roto-Rooter for the Arteries
Statin drugs, which lower LDL (bad) cholesterol, have made a big impact on heart disease, the number-one killer of Americans. "Still, in their finest hour," says Steven E. Nissen, M.D., medical director of the Cleveland Clinic Cardiovascular Coordinating Center, "statins only reduce cardiovascular events by about 25 to 35 percent. That's not good enough. To stop the disease, we've got to do more."
While reducing LDL will stop plaque from continuing to build up in the arteries, it will not reduce the plaque that is already there. But a new treatment may have the power to reverse the disease.
It all started with a group of about 40 related people in Limone sul Garda, Italy, who had extremely low HDL (good) cholesterol but no heart disease. It turns out they had a genetic mutation that created a kind of supercharged HDL, dubbed Apo A-1 Milano, which seemed to keep their arteries clean as a whistle. So Nissen and colleagues worked with Esperion Therapeutics (recently purchased by Pfizer) to bioengineer a synthetic form of that turbocharged HDL. The intravenously administered drug was tested in a small group of men and women. The result: It was found to cause significant reversal of plaque in the arteries. While this small study is very promising, more testing is needed before the drug becomes available to the general public. (Note: There is no opportunity for patients to volunteer for this study.)
A second HDL therapy, also developed by Pfizer, has begun clinical trials. This is a pill called torcetrapib that works by a different mechanism to help raise the patient's own HDL as much as 50 or 60 percent. The two drugs could work together, says Nissen. "We could get a head start on reducing the plaque in a high-risk patient with the powerful but expensive intravenous therapy, and then follow up with the oral drug to sustain the benefit for months or years as needed." Nissen says these therapies will begin to become available in three or four years, assuming study results are positive.
A Medical Lab on a Chip
Remember those Star Trek scenes in which the spaceship's doctor, "Bones," would wave a scanner over a patient to get an instant diagnosis and treatment plan? Now there's an invention that's making personalized medicine a reality. Affymetrix, a Santa Clara, California, technology company, has put the entire human genome -- tens of thousands of DNA strands -- on a glass chip the size of a thumbnail.
Aware that adverse drug reactions kill an estimated 100,000 Americans a year, the company teamed up with Roche Diagnostics to develop the AmpliChip CYP450 Test, a genetic analysis that helps doctors better predict how an individual patient will respond to a certain medication. For example, about one in 250 people have defective genes that put them at higher risk of a dangerous side effect, internal bleeding, if they take the standard dose of the blood thinner warfarin. "The chip can save lives and improve medical care," says Steve Lombardi, Affymetrix's vice president of commercial operations. The test, which is already available in Europe and currently undergoing FDA review in the United States, detects about 30 variations in two genes that regulate how we're affected by many commonly prescribed medications, including some antidepressants, beta blockers, proton pump inhibitors, anti-seizure medications and pain relievers.
To perform the analysis, doctors draw a blood sample and send it to a laboratory that uses the chip and a special reader to analyze the patient's genetic profile. Doctors can then use the results as a guide to customize pill strength, adds Lombardi. "Some people 'burn' drugs very quickly, so the standard dose would have less effect on them, while others metabolize them so slowly that they're at risk of having too much medication build up in their bodies." By pinpointing these differences, the test leads to safer and more effective treatment. The chips are also used in studies to search for the genes responsible for diseases. Instead of studying one DNA fragment at a time, researchers can now analyze thousands of snippets at once, speeding up the quest for cures. In the future, that could lead to treatments to turn off disease-inducing genes -- before we ever get sick.
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