July 15, 2006
Q: Is a bionic human really possible? - Layperson
A: Yes, within limitations. Advances in computer technology, material sciences, laser surgery, and the understanding of chemicals, genes, viruses and bacteria are bringing us nearer to the dream -- or nightmare -- of the bionic being.
This year, Dr Robert Gow, director of the rehabilitation engineering service at the University of Edinburgh produced the results of 35 years of research -- a bionic arm, attached directly to the shoulder, which can be controlled by thought. In 1995 a British company, Blatchfords, produced the first "intelligent knee" -- controlled by a microprocessor and able to detect when the user wants to speed up. Richard Hirons, of the British Association of Prostheses and Ortheses, says that the most important advance within prosthetics during the 1990's has been microprocessor control "through which electrodes can carry instructions from the brain to the artificial limb." Computers are also being used to cure deafness, using cochlear implants married with advanced microchips -- and research on a Low Vision Enhancement System is well under way. American scientists are planning to go beyond this and are already experimenting with attaching electrodes to the nerve centers within the visual cortex. This is bringing us close to the computer vision of robots in science-fiction films... and the question of what makes us human.
When the "Bionic Man" and the "Bionic Woman" were popular on TV in the 1970s, viewers were teased with the scientific possibilities of widely available artificial replacement parts for damaged human organs and limbs.
But with the burgeoning field of regenerative medicine, that vision has become passe, according to a Pitt expert.
"If you think about the future: In 50 years' time, if someone needed a heart valve and if we haven't figured out how to fix that heart without all these devices like a pump or pacemaker, we, as a community, would have completely failed in our opportunity to capture the power of regeneration," said Alan Russell, director of Pitt's McGowan Institute for Regenerative Medicine, which this month is celebrating its second anniversary.
In July 2001, the institute supplanted the former McGowan Center for Artificial Organ Development, expanding its mission to include developing therapies that re-establish tissue and organ function impaired by disease, trauma or congenital abnormalities.
About 170 scientists, engineers and clinical faculty and some 500 adjuncts, students and staff from the Pittsburgh area comprise the McGowan Institute, located at the Biotechnology Center on Technology Drive, with a laboratory building on East Carson Street, South Side. The institute serves as headquarters for faculty developing approaches to the repair or replacement of tissues and organs through the use of cells, genes or other biological building blocks, along with bioengineered materials and technologies. The institute currently attracts about $20 million in National Institutes of Health (NIH) funding. (See sidebar story.) The U.S. Department of Defense (DOD) also is a big player in funding, Russell said, particularly for projects related to diseases caused by weapons of mass destruction.
"If you think about how biological and chemical weapons work, they work through rapid degradation of human function," he said. "For instance with biological weapons, you can't rely on having a vaccine all the time. It would be great if you did, but you need treatments."
Russell said the DOD spends almost as much as the NIH does on tissue engineering. "It's fair to say we have here a more particular interest in defense-related uses of tissue engineering in three areas: wound-healing, musculo-skeletal and cardio-thoracic, and how to use regenerative medicine to address diseases caused by WMDs."
Russell said that medical assisting devices will continue to play a key role, perhaps for the next 20 years, in regenerative medicine. "These devices have taught us so much, and continue to save lives all the time. But the longer-term goal surely has to be to take what we've learned from these devices as a first step to figure out how they can work with cell therapy and tissue engineering to get to a regenerated human that looks and performs just like the regular, healthy human," Russell said.
As an example, Russell cited the work of Robert Kormos, McGowan Institute medical director and director of UPMC's Artificial Heart Program, and his research team. Building on his work in the development of cardio-vascular technologies using ventricular assist devices (VADs) -- battery-powered pumps that support heart function for transplant candidates -- Kormos discovered a half-dozen examples of patients whose hearts regenerated enough to be taken off the organ donor waiting list.
"Dr. Kormos found that the heart was regenerating itself with the help of a device," Russell said. "It's a great example of what we've learned from the devices, but also what we've learned from the heart itself. Unfortunately, no one understands how it happened yet, so that's the wonderful voyage of discovery that needs to take place between now and the future."
While unexplained, the beneficial outcome for Kormos's patients should not be a big surprise, Russell said. Scientists have observed for some time the regenerative powers of the human body.
"What do you do when you break a leg? You functionally unload the leg: You put a cast on it, you keep your weight off it for some period of time and the bone heals and it strengthens," Russell said.
"It's the same for liver injury. As long as you can provide liver function, the liver will regenerate; the lungs are the same way. Those are the two large organs we know can regenerate. So this overarching principle where we say, how can we use a device to functionally unload a damaged organ while it either recovers by itself or is triggered to recover through the application of cell therapy or tissue engineering, is a very exciting principle."
The next steps, Russell said, are to identify what it is about particular patients that make them more disposed to device-assisted regeneration and to learn to predict which patients are going to recover and which will need a transplanted organ. "Undoubtedly, the solution will be something about the nature of the disease itself, and probably, one would guess, it would be related to the patients' behavior once they're on the device."
But getting definitive answers to those questions and harnessing the body's regenerative powers are impossible without interdisciplinary research, Russell stressed, which is why the McGowan Institute was formed as an umbrella organization, with core components of medical devices and artificial organs; tissue engineering and biomaterials; cellular therapies, and clinical translation.
"If you were to ask about how to best use VADs to encourage regeneration, clearly there's going to be a stem cell component, because it's the only way the heart is going to recover. There has to be a device component, so you need electrical engineers, and process-control people figuring out how that pump will work. And you need cell biologists; in this case, they have to make their preparations compatible with a pump, and not just with living tissues. And you need pre-clinical and clinical protocols."
Russell gave other examples of cutting-edge research at the McGowan Institute, including:
* The research of Stephen Badylak, director of a McGowan Institute's new Center for Pre-Clinical Tissue Engineering and research professor in the medical school's Department of Surgery, who came to Pitt last January as one of the institute's outstanding recent recruits, Russell said.
"Think about what part of your body gets damaged the most," Russell said. "It's the stomach that gets damaged constantly, and has to renew itself all the time. What Dr. Badylak did was take the premise that de-cellularized stomach material would retain its regenerative signals no matter where it's put. And he proved the premise, using the lining of a pig's stomach."
Badylak took stomach material, removed the cells, sterilized the material and demonstrated that the material induces wound healing in humans.
"There are now 160,000 human patients worldwide who have benefited from this, making it the most successful tissue engineering project in the world as measured by patient-user number," Russell said.
* Another new McGowan recruit, professor of surgery Jšrg Gerlach, is recognized for his innovative work on biohybrid liver design, Russell said. By building bioreactor systems that combine synthetic components with human cells, Gerlach created support therapies that boost a patient's own healing process, while a defective liver rests.
Analogous to a kidney dialysis machine, the biohybrid liver gives the liver support, which facilitates natural healing.
"He and his team are now doing the same thing here with stem cell bioreactors," Russell said, "asking the question: Can you take adult-derived stem cells and can you culturize them in this three-dimensional complex bioreactor and have them turn into whatever tissue you want by applying the lessons he learned previously in his liver studies? This is very exciting and promising research," Russell added.
* A third 2003 McGowan Institute recruit, Bruno Peault, is internationally recognized for his stem cell research, Russell said.
A stem cell developmental biologist with a joint appointment in pediatrics and cell biology at Pitt, Peault's research includes identification, characterization and purification of several categories of human stem cells.
His research has focused on the characterization of human hematopoietic stem cells, and he is credited with the development of new assays for human stem cells in immunodeficient mice.
Recently, this assay system has identified the first population of stem cells in the human respiratory epithelium. His model also has been modified to create the first system in which defective lymph nodes can be maintained intact and functional for extended periods of time.
January 3, 2002: Rods and Cones. Millions of them are in the back of every healthy human eye. They are biological solar cells in the retina that convert light to electrical impulses -- impulses that travel along the optic nerve to the brain where images are formed.
Without them, we're blind.
Indeed, many people are blind -- or going blind -- because of malfunctioning rods and cones. Retinitis pigmentosa and macular degeneration are examples of two such disorders. Retinitis pigmentosa tends to be hereditary and may strike at an early age, while macular degeneration mostly affects the elderly. Together, these diseases afflict millions of Americans; both occur gradually and can result in total blindness.
Above: "Eye chart with eyes." Copyright Philip Kaake. All rights reserved.
"If we could only replace those damaged rods and cones with artificial ones," says Dr. Alex Ignatiev, a professor at the University of Houston, "then a person who is retinally-blind might be able to regain some of their sight."
Years ago such thoughts were merely wishful. But no longer.Scientists at the Space Vacuum Epitaxy Center (SVEC) in Houston are experimenting with thin, photosensitive ceramic films that respond to light much as rods and cones do. Arrays of such films, they believe, could be implanted in human eyes to restore lost vision.
"There are some diseases where the sensors in the eye, the rods and cones, have deteriorated but all the wiring is still in place," says Ignatiev, who directs the SVEC. In such cases, thin-film ceramic sensors could serve as substitutes for bad rods and cones. The result would be a "bionic eye."
The Space Vacuum Epitaxy Center is a NASA-sponsored Commercial Space Center (CSC) at the University of Houston. NASA's Space Product Development (SPD) program, located at the Marshall Space Flight Center, encourages the commercialization of space by industry through 17 such CSCs. At the SVEC, researchers apply knowledge gained from experiments done in space to develop better lasers, photocells, and thin films -- technologies with both commercial and human promise.
Below: A schematic diagram of the retina -- a light-sensitive layer that covers 65% of the interior surface of the eye. SVEC scientists hope to replace damaged rods and cones in the retina with ceramic microdetector arrays. Image courtesy A. Ignatiev.
Scientists at Johns Hopkins University, MIT, and elsewhere have tried to build artificial rods and cones before, notes Ignatiev. Most of those earlier efforts involved silicon-based photodetectors. But silicon is toxic to the human body and reacts unfavorably with fluids in the eye -- problems that SVEC's ceramic detectors do not share.
"We are conducting preliminary tests on the ceramic detectors for biocompatibility, and they appear to be totally stable" he says. "In other words, the detector does not deteriorate and [neither does] the eye."
"These detectors are thin films, grown atom-by-atom and layer-by-layer on a background substrate -- a technique called epitaxy," continues Ignatiev. "Well-ordered, 'epitaxally-grown' films have [the best] optical properties."
Crafting such films is a skill SVEC scientists learned from experiments conducted using the Wake Shield Facility (WSF) -- a 12-foot diameter disk-shaped platform launched from the space shuttle. The WSF was designed by SVEC engineers to study epitaxial film growth in the ultra-vacuum of space. "We grew thin oxide films using atomic oxygen in low-Earth orbit as a natural oxidizing agent," says Ignatiev. "Those experiments helped us develop the oxide (ceramic) detectors we're using now for the Bionic Eye project."
Right: In 1996, during shuttle mission STS-80, astronauts use Columbia's robotic arm to deploy the Space Vacuum Epitaxy Center's Wake Shield Facility.
The ceramic detectors are much like ultra-thin films found in modern computer chips, "so we can use our semiconductor expertise and make them in arrays -- like chips in a computer factory," he added. The arrays are stacked in a hexagonal structure mimicking the arrangement of rods and cones they are designed to replace.
The natural layout of the detectors solves another problem that plagued earlier silicon research: blockage of nutrient flow to the eye.
"All of the nutrients feeding the eye flow from the back to the front," says Ignatiev. "If you implant a large, impervious structure [like the silicon detectors] in the eye, nutrients can't flow" and the eye will atrophy. The ceramic detectors are individual, five-micron-size units (the exact size of cones) that allow nutrients to flow around them.
Artificial retinas constructed at SVEC consist of 100,000 tiny ceramic detectors, each 1/20 the size of a human hair. The assemblage is so small that surgeons can't safely handle it. So, the arrays are attached to a polymer film one millimeter by one millimeter in size. A couple of weeks after insertion into an eyeball, the polymer film will simply dissolve leaving only the array behind.
The first human trials of such detectors will begin in 2002. Dr. Charles Garcia of the University of Texas Medical School in Houston will be the surgeon in charge.
"An incision is made in the white portion of the eye and the retina is elevated by injecting fluid underneath," explains Garcia, comparing the space to a blister forming on the skin after a burn. "Within that little blister, we place the artificial retina."
Left: These first-generation ceramic thin film microdetectors, each about 30 microns in size, are attached to a polymer carrier, which helps surgeons handle them. The background image shows human cones 5-10 microns in size in a hexagonal array. Image courtesy A. Ignatiev.
Scientists aren't yet certain how the brain will interpret
"It's a long way from the lab to the clinic," notes Garcia. "Will they work? For how long? And at what level of resolution? We won't know until we implant the receptors in patients. The technology is in its infancy."
Ignatiev has received over 200 requests from patients who learned of the studies from earlier press reports. "I'm extremely excited about this," he says. He cautions that much more research is needed, but "it's very promising."
Real flesh-and-blood must be reconciled with the engineering of the artificial component. For instance, if an artificial arm can lift 4,000 lbs., the human body can not handle this much weight. At the very least, the skeletal system would have to be reinforced. To run faster than 25- 30 mph, the heart, circulatory and respiratory systems would have to be enhanced. As long as the artificial component mimics closely, the flesh-and-blood component, a bionic person is a very real possibility.
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