Roanoke Times
Copyright (c) 1995, Landmark Communications, Inc.
DATE: SUNDAY, February 6, 1994 TAG: 9402060190
SECTION: HORIZON PAGE: C-1 EDITION: METRO
SOURCE: By ROBERT WHITAKER
DATELINE: ALBANY, N.Y. LENGTH: Long
The message: Medical wizardry would one day be able to turn us into modular creatures. The surgeons of tomorrow would be able to replace any number of body parts.
That scenario, cloaked in Hollywood hype, was visionary. But we are in fact rapidly headed toward an era when the medical toolbox will include a vast array of substitute body parts, ranging from "all natural" organs grown in the laboratory (or in other animals) to artificial limbs that provide sensory feedback to an amputee's brain.
"We are not at the point we are able to replace body parts wholesale," said Alan Snyder, an associate professor of bioengineering at Penn State University, who is doing research on an artificial heart, "but we have made big strides, and bit by bit, gained in our understanding of what is necessary to get along with the body, and what we can and can't do."
Our society, of course, has already begun moving full-steam toward the replacement of failing body parts. The first total hip replacement was done in 1938. By 1988, more than 11 million people in this country had permanent medical implants - hips, knees, heart valves, pacemakers and lenses for the eye.
But the body-parts repair shop of today, compared to what is coming, is like comparing an old-fashioned corner grocery store to an amazing superstore.
Scientists today are discovering how to grow tissues and organs - skin, liver, intestine, gum, eye tissue, cartilage, bone, and even cartilage and bone together. They are designing biohybrid organs - live tissue enclosed in an artificial membrane - to replace the pancreas and other failing endocrine glands. Devices are being built to restore hearing to the deaf, and research is being done of ways to give sight to the blind. An artificial heart designed to be a permanent replacement is expected to be on the market by the turn of the century.
The final frontier: Scientists are looking at ways to grow new brain tissue for repairing damage from age-related diseases.
"Even as recently as two or three years ago, that kind of idea would have sounded absurd," said Ron McKay, a biologist at the National Institutes of Health, speaking about growing new brain tissue, the subject of his research. "Now it's quite plausible."
All of this technology is going to change our sense of what it means to grow old. We will see ourselves more as aging machines, with interchangeable parts. Just as we bring a car in for a new carburetor, a new fuel pump, we will come to the doctor for a new heart, a brain graft. Keep us fit, doctors, until the very end.
"Right now it seems to me that we are beginning to be able to artificially maintain biological systems, and the line between living and non-living technological constructs is disappearing," said Gregory Stock, author of "Metaman," a book that looks at the ways science is changing humankind.
If there is one organ replacement that has always caught the public's imagination, it is the heart. As poets have long told us, the heart is symbolic - it is part of what makes us who we are. Installing a plastic heart seems not so much to represent the repair of an organ as a step across a line much more profound: the merging of man and machine.
Artificial hearts around today, such as the Jarvik heart, were never meant to be permanent. They were designed to be temporary bridges for people with failing hearts waiting for a heart transplant. But three research labs in the country are developing plastic hearts that, once they are approved for human use, will come with a five-year guarantee.
All three hearts, which are being tested in animals, share certain design elements. They are portable, powered by external batteries that transmit energy across the intact skin and can pump up to nine liters of blood in a minute - enough blood to sustain a light jog. An internal battery can power the heart for a short period, letting the person remove the external battery pack for hygienic and other personal reasons.
At Penn State University, Snyder and his colleagues have kept dairy calves alive for as long as five months with one of their artificial hearts. The heart weighs a little less than two pounds, has variable pumping speeds and a reversible electromechanical drive for alternately pumping each of the heart's chambers.
Estimated cost: $100,000.
"In the animal lab, you operate and the next day you see the animal standing and eating hay, and yet it is not often you stop to think he doesn't have a natural heart any more and basically doesn't seem any different," Snyder said.
The Heart Lung and Blood Institute, which is funding this research, estimates that artificial hearts may be implanted in 10,000 to 20,000 people in the U.S. each year, starting at the turn of the century. In another 50 years or so, said institute research director John Watson, people with failing hearts may not get a plastic replacement but one made of natural tissue and grown in the laboratory.
"We have the potential for biologically replacing the heart," he said.
As wild as that possibility may seem, researchers are already learning how to grow simpler organs, such as liver, skin and cartilage. This enterprise of tissue engineering, as it has come to be known, is a field that has exploded in the past few years.
"My vision is that this kind of technology - tissue engineering - is going to change the way we do things in surgery," said Dr. Joseph Vacanti, chief of transplantation at Children's Hospital in Boston and one of the pioneers in this field. "The whole issue of organs becoming available from brain-dead donors will be history."
During the past few years, Vacanti and his collaborators have developed a core tissue engineering technology, which they have successfully used to grow several types of tissue.
From a small sample of donor tissue, they isolate the primary cell type in the tissue (in cartilage, for example, these cells are called chondrocytes) and multiply the cells in culture. They then seed the larger mass of cells onto a mesh-like scaffolding of biodegradable fibers, which can be woven into any desired shape. The cells, trapped in the mesh, continue to divide and multiply, growing into the three-dimensional shape of the scaffolding.
The seeded scaffolding, during this period, can be kept in a laboratory incubator or implanted beneath the skin. The scaffolding gradually degrades, and is replaced by structural proteins and other supporting matrix material secreted by the cells. All that is left after the scaffolding has disappeared is natural tissue.
In essence, the ultimate goal for these researchers is to mimic nature's blueprint for growing tissues.
"How do we go from an embryo to the complete structure? It comes down to understanding life itself," said Robert Langer, a chemical engineering professor at Massachusetts Institute of Technology, who is working with Vacanti.
In a similar vein, researchers are learning to build "biohybrid" substitutes for hormone-secreting glands. They are doing so by placing the cells that secrete the needed hormone - such as the insulin-secreting islet cells of the pancreas - inside a selectively permeable membrane.
The membrane is made permeable to the nutrients, wastes and the hormones the cells secrete, but - through a trick of polymer chemistry - impermeable to immune-system proteins.
The beauty of a biohybrid gland is that because the transplanted cells are isolated from attack by the immune system, the donor cells do not have to come from a human donor, but can come from an animal. In trials with dogs, biohybrids made with pig cells have proven an effective treatment for diabetes.
The medical cabinet, of course, already contains a treatment for diabetes: insulin. The advantage of a biohybrid pancreas is that it will secrete insulin in response to glucose levels in the blood, a fine-tuned response that is much healthier than injecting insulin into the body several times a day.
"It functions the way a normal pancreas functions," said Dr. William Chick, president of Biohybrid Technologies in Shrewsbury, Mass., a biotech company that expects to begin human clinical trials of its biohybrid pancreas within two years.
The same approach may be used to treat Parkinson's disease. This motor ailment is the result of the death of brain cells that secrete the neurotransmitter dopamine. Put cells genetically engineered to produce dopamine inside a permeable membrane, and this dopamine-producing packet could be implanted in the patient's brain.
"Whenever you have a disease that results from inappropriate or inadequate secretion of compounds that you need, the hope is you can use this approach," said Clark Colton, a professor of chemical engineering at Massachusetts Institute of Technology who is working on biohybrid organs.
The body shop of the future, however, will be filled with far more than a supply of biological replacements for tissues and organs. As the artificial heart research suggests, what can't be regrown will be remade - and with materials that aren't simply tolerated by the body, but biologically welcomed.
The use of artificial hips, knees, and other joints has been one of medicine's biggest success stories during the past few decades. Their widespread use has been credited as a key factor in sharply declining disability rates among the elderly. One recent study, for example, found that the number of elderly persons requiring personal assistance declined 10 percent from 1982 to 1989, even as the total elderly population increased.
However, these joints tend to loosen over time. The body's internal environment is highly corrosive and gradually the cement used to bond the metal implant to the bone dissolves.
One possible solution to this problem is to coat the implants with a ceramic, hydroxylapatite. This compound is similar to minerals in the bones and teeth, and so it is treated by nearby bone as a friendly intruder.
"The cells are fooled," explained Robert Doremus, chairman of the materials engineering department at Rensselaer Polytechnic Institute in Albany. "They think it belongs there. It is a natural material. The cells grow up against it and bond to it."
One part of the body appears to be resistant to repair - the nervous system. Yet even here, there are glimmers of success that hint of future wonders.
The most notable example is the recent invention of cochlear implants that restore a limited sense of hearing to the deaf. This device could be the first of many 21st century prosthetic implants for repairing damaged nerve circuits.
"All of this work will translate to stimulating other systems, whether the visual system, or the motor system," said Donald Eddington, director of a cochlear implant research laboratory at Massachusetts Eye and Ear Infirmary in Boston.
In a healthy ear, Eddington explained, sound waves cause hair cells in the cochlea, which is a fluid-filled, snail-shaped chamber, to vibrate. Different frequencies affect hair cells in different parts of the cochlea, and it is this pattern of activity, transmitted to the brain via 30,000 nerve fibers attached to the hair cells, that is interpreted by the brain as a specific sound.
However, a common cause of deafness is the loss of the hair cells. A cochlear implant makes up for this loss by sending an electric signal to electrodes inside the cochlea. Incoming sound waves are broken down into different frequencies, and each spectrum of energy is routed to the electrode near the nerve fibers normally excited by that frequency. In this manner, normal excitatory patterns in the cochlea are mimicked.
"The idea is to trick the brain into thinking it is hearing. It doesn't care how you excite those activity patterns; it just wants to see those patterns," Eddington said.
In a similar manner, researchers at the National Institute of Neruological Disorders and Stroke are trying to develop a visual prosthesis for restoring sight to the blind. A blind person would wear a miniature television camera, which would send signals to electrodes implanted into the visual cortex in the back of the brain. Experiments have shown that stimulation of this area of the brain in blind people enables them to discern patterns of light.
All of this work on replacement parts - livers regrown, plastic hearts implanted and nerve circuits repaired - may make us a little nervous. How many parts can we replace before we start to feel less than fully ourselves? That question may become particularly relevant when we start going to the body shop for the ultimate repair: brain grafts.
Once we reach adulthoood, our brain cells neither divide nor regenerate. Our adult life is made up of a steady loss of neurons, and if this loss is hastened abnormally by disease, it leads to Alzheimer's and Parkinson's. But a handful of researchers are looking at ways to replace this damaged tissue.
McKay, at the National Institutes of Health, is one of the pioneers in this field. He has shown that he can take fetal tissue stem cells - these are cells which have yet to differentiate into a particular type of cell - and get them to grow into brain cells of various types. He also has shown that he can expand the fetal tissue cells in culture, and thus he could, in theory, grow a steady supply of brain cells for transplants.
Moreover, in experiments with rats, he has shown that these transplanted brain cells will form synapses, which means they are hooking up in an integrated way with surrounding brain tissue. This research suggests that it may one day be possible to rebuild the part of an aging brain damaged by disease.
"The ideal situation is to actually truly reconstruct, at a cellular level, what is missing," McKay said.
As impressive as all of this research may seem, few of these substitute parts fully restore function, and so it would be wrong to think that doctors one day will be able to replace body part after body part until little of the original person is left. At the same time, however, the science of "substitute" medicine is very much in its infancy, and, in the decades ahead, we are sure to become much more adept at repairing our aging bodies.
"There is something in our genetic makeup which makes us mortal, and replacement parts will not change that and make us immortal," said Dr. Pierre Galletti, professor of medical science at Brown University. "The goal of substitute medicine should be to have people die as physically young as possible" at the latest age possible.
by CNB