From Repair or Replace
A new era in medicine is dawning. And it's just in time for a culture that worships youth and beauty, that has witnessed a parade of scientific and technological triumphs, and that believes in the American Dream, with its endless opportunities for self-renewal. We don't just hope to stay young and vital, healthy and happy, forever -- we expect it. What is surprising is how far medical science has come toward meeting those expectations. Now there are treatments to repair or replace tissues and organs, therapies that compensate for defective genes, devices that stand in for failing body parts, and treatments to keep us thin and wrinkle-free.Rebuilding the heart. The motto of this new era might be "Repair it if you can. Replace it if you can't." Ron Trachtenberg, now 59, of Stoneham, Massachusetts, needed some repairs. At 34, he was a self-described Type A person with a young family and a burgeoning accounting practice, when he was diagnosed with severe coronary artery disease. By 46, after a quadruple bypass operation, a heart attack and a second bypass, his poor health had forced him to sell his business. For years afterward, he mostly stayed home, where his wife and two adult children helped care for him. He experienced the severe chest pain of angina as often as three times a day. "It felt like an eight-ton elephant," he says.
Trachtenberg's cardiologist referred him to Douglas Losordo, MD, chief of cardiovascular research at Caritas St. Elizabeth's Medical Center in Boston. Losordo had begun a clinical trial testing an experimental stem-cell therapy on terminal heart disease patients. (Enrollment is now complete.) Although it's a blind, placebo-controlled study and no one can yet confirm that Trachtenberg received the treatment, it's most likely that in February 2004, he was given a drug to spur production of stem cells in his bone marrow. Then those stem cells were harvested from Trachtenberg's blood. Losordo snaked a catheter through an artery into Trach-tenberg's heart, injecting his stem cells into a part of his heart muscle that survived but would not contract. Today, Trachtenberg's heart is pumping better than it has in at least a decade. In the past year, he's had just three severe angina episodes. He walks half a mile a day, and he flew to Florida with his wife on vacation -- his first flight in ten years. "I'm a father and a husband again," he says.
He's also lucky. Heart attacks leave patients with a dead region of heart muscle, and current medications succeed only in keeping neighboring areas of heart muscle alive. The stem-cell treatment Trachtenberg received was designed to get surviving but noncontracting heart muscle back into action. Other patients in Losordo's clinical trial -- a 24-person test to make sure the treatment is safe -- are feeling better too. Clinical trials in Germany showed that stem-cell therapy restores some of the heart's lost pumping capacity in severely ill cardiac patients. But it won't be available in most cardiac units until doctors conduct a large trial that convinces the FDA it's effective.
New Technology Triumphs
Engineering eyes. When disease or injury claims entire tissues, scientists called tissue engineers can now grow replacements in the lab. Last year, Kohji Nishida, MD, and his co-workers at Japan's Osaka University Medical School Department of Ophthalmology, snipped a tiny piece of tissue from inside the cheek of a 58-year-old man who was nearly blind from a rare eye disease. They grew stem cells from that tissue into a sheet in a culture dish, transplanted the sheet onto the damaged cornea, and covered it with a soft contact lens. Within six weeks, the man could see clearly, and his sight remained clear a year later.Skin, knees and organs. Doctors can now grow enough replacement skin from a postage-stamp-sized biopsy to cover the entire body of a patient with severe burns. For that procedure, they can use Epicel, a tissue-engineered skin from Genzyme Biosurgery in Cambridge, Massachusetts. Genzyme's Carticel, a lab-grown human knee cartilage, gives orthopedic surgeons an alternative way to treat injured knees.
Anthony Atala, MD, professor of surgery at Wake Forest University, has used lab-grown cartilage to cure incontinence. He snips a piece of cartilage from an ear and grows it into a precisely shaped piece of cartilage that bulks up the opening from the bladder. He's also grown a human bladder, and if the FDA approves, he'll begin testing it as a replacement bladder for patients who have lost theirs to cancer or injuries.
Artificial kidney. Hybrid devices, part conventional prosthetic and part lab-grown cells, are being tested as a treatment for desperately ill patients. David Humes, MD, a professor of internal medicine at the University of Michigan in Ann Arbor, has created a so-called bio-artificial kidney to treat patients whose kidneys have suddenly failed due to blood loss. More than 70 percent of such patients now die, but they usually recover if they survive the initial crisis. Humes grows human kidney cells in a filtering device the size of two stacked soda cans. Humes's bio-artificial kidney seems to be saving more lives than the conventional treatment, according to a trial that so far includes 50 patients. His ultimate goal, which is at least five years off, is a wearable bio-artificial kidney for the 375,000 U.S. patients with end-stage kidney disease who now undergo dialysis. Tissue engineers hope lab-grown organs will one day alleviate the shortage of transplantable organs so people won't have to die waiting for them.
High-tech limbs. Mechanical prosthetics are improving by leaps and bounds, too, thanks to technological advances and the U.S. Department of Defense, which is sparing no expense to offer amputee Iraq war vets the latest in high-tech artificial limbs. The SensorHand Speed, from Otto Bock HealthCare, for example, adjusts its grip automatically, and is the first to open and close quickly enough to allow patients to throw and catch a baseball. The Rheo Knee from Ossur, an Icelandic company, has a special metal-containing fluid that thickens when needed to adjust the knee's shock-absorbing ability. That helps patients do difficult tasks like walk down stairs. "You can program them to be any knee you want them to be," says Joseph Miller, chief clinical and research prosthetist at Walter Reed Army Medical Center in Washington, D.C.
Boosting the Brain
Implants. Among the most amazing new medical devices are those that stimulate nerves electrically. "Virtually every function in the body is controlled by electrical signals from the nervous system, so neural stimulation is potentially able to influence a huge range of functions," says Gerald Loeb, MD, professor of biomedical engineering at the University of Southern California.Jackie Brown can attest to the power of electricity. Brown, 50, of Duncanville, Texas, a suburb of Dallas, suffers from Parkinson's disease. A drug called Sinemet helped control her symptoms: tremors, impaired balance, slow and stiff movements. But each night, when the medication wore off, the tremors would start. As she lay on her bed, her husband, Guy Brown, a six-foot-four, 230-pound former linebacker for the Dallas Cowboys, would sometimes lie on top of her legs to keep her from helplessly thrashing about. "I could push him off the bed," she recalls. "It would cramp and shake that bad."
In March 2004, doctors drilled two symmetrical nickel-sized holes on each side of Brown's skull. In each, they inserted a thin electrode into a pea-sized structure called the subthalamic nucleus, deep in each hemisphere of the brain. Then they surgically threaded its wires under the skin of Brown's head and neck to an implanted, matchbook-sized pacemaker in her chest, much as electricians run wiring inside a wall. They spent two weeks programming the device, and weaned her off much of the Sinemet. Brown now does t'ai chi, lifts weights, drives her car and goes to bed like everyone else. "It's a miracle," she says.
Deep brain stimulation (DBS) "is an opportunity to help give people back their dignity, their control, their hope," says Malcolm Stewart, MD, the John and Patricia Fox chair of neurology at Presbyterian Hospital of Dallas, who was part of a three-doctor team that treated Brown. A clinical trial published in 2003 in the New England Journal of Medicine shows that DBS alleviates symptoms five years after it's implanted. But it takes $100,000 and an expert team of doctors to install a DBS system and program it, and brain surgery can lead to infection, stroke or seizure. What's more, the disease continues to damage the brain, Stewart says. Still, neural stimulators akin to Brown's are being used or tested to ease symptoms of an astonishing array of illnesses, including migraines, obesity, epilepsy, Tourette's syndrome and severe depression.
Neural prosthetics. Other new-generation neural devices are true prosthetics -- they carry out a brain or neural function lost to disease or injury. Cochlear implants, the first brain prosthetics, have given deaf people back the ability to understand speech and are now used by 60,000 deaf and hearing-impaired people worldwide. A retinal prosthetic developed at the University of Southern California has restored rudimentary vision, including, for several blind people, an ability to see light and distinguish between a cup, a plate and a knife. Loeb's team is testing remote-controlled injectable muscle implants the size of long-grain rice that impel flaccid, paralyzed muscle to move. So far, in a small trial, the device, called a BION (short for bionic neuron), has spurred paralyzed shoulder muscles to contract in stroke patients. It holds paralyzed arms in their sockets, reverses shoulder pain, and could keep muscles working until the stroke victim regains his ability to direct his arm, says Loeb. If used soon after a stroke, the BION could also prevent muscle atrophy in the first place.
Loeb emphasizes that no matter how promising such a device is, it will be widely used only if a medical device company commits to producing it, insurance companies agree to pay for it, and doctors get comfortable prescribing it. That took 20 years for cochlear implants, he says, so be patient.
Battling Genetic Disease
Personalized genetic diagnosis and therapy. Say you're young and healthy, and you go in for a routine physical. Your doctor takes a blood sample and has it shipped to a lab. There, a medical technologist places your serum sample on a glass chip the size of a postage stamp. That gene chip might contain up to 50,000 microscopic spots -- each with one of the genes in the human genome. When the doctor calls you with the results, she'll tell you which of thousands of human diseases you're at risk for. If you have a defective gene that's placing you at risk for disease, she might treat you with a healthy version of the gene to make up for it, keeping you out of harm's way.Soon, such diagnoses and treatments could be routine, says Mark Kay, MD, a professor of genetics at Stanford University School of Medicine and president of the American Society of Gene Therapy. "In five years, you may be able to go to referral centers and get gene therapy," he says. Although gene therapists have talked like that for a while, and the field has tremendous promise, so far they have demonstrably cured humans of just one disease: severe combined immunodeficiency (SCID). Known as the bubble-boy disease, it decimates the immune system and causes children to die young from infections. While the treatment looks promising, the virus used to deliver the gene in one trial may have activated a gene that causes cancer.
Is it safe? Such safety issues have dogged gene therapy. But gene therapists are pressing on. More than a dozen advanced clinical trials are underway that use genes to treat a variety of cancers, and other trials are ongoing for multiple sclerosis, AIDS and cystic fibrosis. Dr. Losordo has also begun a large trial of a gene therapy that seems to help patients regrow blood vessels that supply the heart -- "grow your own bypass, if you will," he says. "It's a very exciting time."
Nanotechnology. To get around the safety problems in gene therapy -- as well as the side effects of conventional drug therapies -- scientists have begun tapping nanotechnology for solutions. Most nanotechnology-based therapies being studied now remain at least five years from the clinic, but scientists have begun using them to tackle cancer in mice. Robert Langer, ScD, a professor of chemical engineering at MIT, and Daniel Anderson, PhD, a research associate, have taken a plastic-like molecule called a polymer, much smaller than a cell, wired it with a gene for a bacterial toxin, and sent it, like a suicide bomber bent on destruction, into a nasty human prostate tumor growing in a mouse. When all was said and done, the suicide polymers had shrunk 40 percent of the tumors and slowed or stopped the rest.
Polishing the Outer You
Once upon a time, people got old. Their skin wrinkled, their hair turned gray, they gained a few pounds, and gravity took its toll. They looked, well, old. We don't accept that anymore. And, thanks to new weight-loss treatments and a wealth of recent advances in cosmetic and plastic surgery, we may not have to.Weight-loss wonders. We're more overweight than ever, but new weight-loss techniques are raising hopes for the severely obese. Gastric bypass surgery and laparoscopic banding work well to combat obesity, and gastric pacemakers look promising, says Louis Aronne, MD, director of the comprehensive weight-control program at New York-Presbyterian Hospital and president of the North American Association for the Study of Obesity. And soon there may be a fat-fighting drug that really works. In a clinical trial of more than 1,500 obese and overweight people, daily doses of rimonabant (Acomplia), made by the French company Sanofi-Aventis, helped people lose 10 to 15 percent of their body weight and reduce their waistlines by 1.6 inches more than placebo pills did.
Cosmetic enhancement. Last year, Nancy Curren, 61, of San Diego, California, was a "retired schoolteacher looking for my next passion in life." She decided to do something about the wrinkles around her eyes, roughened skin and brown spots caused by years of sun exposure. "We all age. No matter what we're feeling inside, the world starts to judge you," she says. So she underwent a laser-ablation procedure called Fraxel to remove signs of aging. Fraxel patients are treated five or six times with a grid of pinpoint laser beams that zaps tiny spots on the skin. That triggers the skin's inner layer, the dermis, to produce the collagen that makes skin look full and smooth, says Cameron Rokhsar, MD, a cosmetic surgeon, now at the New York Aesthetic Center, who treated Curren. The treatment tightened her skin, improved its texture, removed the photodamage and made wrinkles less visible. The results were "tremendous," she says.
New technologies, all introduced in the past few years, are changing the face of plastic and cosmetic surgery, allowing surgeons to nip, tuck, smooth and plump with finer control and less downtime than ever before. Cosmetic and plastic surgeons now use easy-to-inject fillers like Restylane to plump lips, barbed sutures to allow outpatient face-lifts, Botox to relax wrinkles, Thermage to lift and tighten skin, and ultrasound devices to melt small bulges of fat. "All of these things are less invasive ways of facial rejuvenation," says V. Leroy Young, MD, chairman of the Task Force for Emerging Trends of the American Society for Aesthetic Plastic Surgery.
What's Next
The best gene therapies, replacement body parts, medical technology, and all the fat sucking, skin polishing and wrinkle removing in the world all just treat symptoms. The cells and tissues that make up our body still age, decay and die. "We know of no intervention that will slow, stop or reverse the aging process in humans," says Leonard Hayflick, PhD, professor of anatomy at the University of California, San Francisco, School of Medicine, who's the éminence grise of aging studies. Also, lifesaving technologies and treatments don't come cheap, and sometimes terrible side effects emerge. "We will face some very difficult choices," says Thomas Murray, PhD, president of the Hastings Center in Garrison, New York, a think tank that explores ethical issues in biotechnology and health care. Fair enough. But perhaps it's OK, for now, to step back and marvel at just how far we've come.
Despite the continuing debate over stem cells, doctors have actually been giving them to patients for more than two decades. They enable bone-marrow transplants to replenish blood and immune cells in patients with leukemia, lymphoma and rare blood diseases.
Stem cells are useful because they're youthful -- vigorous, immature, with the potential to mature into blood, nerve, heart and other tissues. In the past decade, scientists have discovered stem cells that transform into a variety of other tissues. Clinical trials using a variety of adult stem cells are underway to treat injured knee tissue, a variety of cancers and, soon, amyotrophic lateral sclerosis (Lou Gehrig's disease). But they grow rapidly, and no one is sure they won't turn into cancer cells after a decade or more in the body. So for now, they're being used only in the sickest patients.
The most versatile -- and controversial -- stem cells come from days-old human embryos in the freezers of in vitro fertilization clinics. These cells can mature into any of the body's 200 or so cell types.