The African green monkey stands in the classic pose of Parkinson's disease: hunched over, constant tremor in its arms, hands and head, and barely able to move toward the food dropped into its cage.
The scene on the videotape monitor shifts; the same monkey moves with ease and without the tremor or stooped posture. One difference: a line of suture scars splits the center of the monkey's recently shaved scalp.
The monkey has had, in a sense, a brain transplant. A clump of dopamine-producing brain cells taken from a monkey fetus have been implanted in the adult African green monkey's brain. Once in place, the cells continued to manufacture and secrete dopamine, the molecular essense of movement.
The videotapes -- produced by researchers at Yale University and the University of Rochester and shown during a New York Academy of Science symposium on brain transplants here last week -- demonstrate that transplants can repair damaged brains in monkeys. If similar experiments work in humans, they offer hope of a new treatment for disorders such as Parkinson's, in addition to Alzheimer's disease and other dementias.
But so far, attempts to transplant living tissues into the brains of four Swedish patients failed to substantially or permanently reverse the symptoms of their Parkinson's disease. The recent experiments in monkeys, however, have shown that technical advancements -- such as the kinds of tissues transplanted and where those transplants are placed in the brain -- may make the transplants more successful.
The first American attempts to treat humans with Parkinson's disease could come as early as next year, said Dr. Richard J. Wyatt, chief of the adult psychiatry branch at the National Institute of Mental Health. But it will be a long time before this technique becomes a routine treatment for brain disorders such as Parkinson's. The rigidity and paralysis of Parkinson's disease occur when dopamine-producing neurons die in the aging brain. The disorder afflicts some 500,000 Americans.
Transplanting chunks of tissue into animal brains is not new. A University of Chicago researcher first successfully grafted tissue into a rat in 1903. No one has ever proposed a whole brain transplant, as surgeons now swap hearts, livers and kidneys.
The central nervous system -- the brain and the spinal cord -- are much like an electric company with dozens of power plants and a complicated network of distribution lines and substations. If a power station burns out and interrupts the flow of electricity in one section of the entire system, electricians simply reroute electricity and repair the power plant. They don't replace the entire system.
Like the electricians, neurosurgeons try to fix the limited damage in a portion of the brain, not replace it entirely. But the living cells transplanted into the brain can't just be taken off the shelf. Cells for transplanting may come from three sources: The patient's own adrenal gland, because certain adrenal cells become dopamine-producing neurons when placed in the brain; the brains of aborted fetuses; and cancer cells growing in labortory cultures that can be transformed into mature nerve cells with certain drugs.
The first surgical attempt to cure Parkinson's disease in a human occurred on March 30, 1982, at the Karolinska Institute in Stockholm. Dr. Erik-Olof Backlund, a neurosurgeon now at the University of Bergen in Norway, reviewed for the New York conference how the Swedish team transplanted adrenal cells into the brain of a 55-year-old man with an eight-year history of parkinsonism. The man had rapidly deteriorated during the previous year.
Under local anesthesia, the man's head was secured in a metal frame and a CAT scan was performed to locate the region of the brain to be implanted. Under general anesthesia, surgeons removed one of the man's adrenal glands, which sit atop the kidneys.
Surgeons cut portions of the gland into small sections and loaded them into a blunt metal tube. The surgeons guided the tube through a hole in the skull to an exact location within the brain identified on the CAT scan.
The patient woke up promptly, but his condition had not changed, the Swedes reported. About a day later, he reported a slight improvement in his ability to move his arm, but the improvement lasted only one week.
Three more patients underwent surgery on May 5, 1983, March 19, 1985, and March 20, 1985, all with generally the same results.
"There were no long-term effects on any of the tests and after six months, there was no difference from before the transplant," said Dr. Olle Lindvall, a neurologist from the University of Lund in Sweden. "We did not see any harmful effects of transplanting the cells in the brain .
"The findings closely resemble what happened in animals -- acute release of dopamine with chronic but low-level effects for six months. We believe that the data are promising and that it will be possible to develop a transplant for Parkinson's disease."
Others were less optimistic. "We are dealing with rather disappointing results," Dr. Pedro Pasik of Mount Sinai School of Medicine said of the Swedish results.
Even Lindvall admitted that "we cannot help the patients with the renal medulla transplant. Today, we do not have a transplantation therapy."
With the apparent failure of the adrenal cell to brain transplants in humans, attention has turned to transplanting fetal cells in monkeys. The results at Emory University in Atlanta, Yale University and the University of Rochester have all been promising.
Researchers at the National Institute of Mental Health have been experimenting on monkeys for the last six years.
"Our initial success in monkeys was terrible," said NIMH's Wyatt. "Initially, we could not get fetal cells to grow. Now we are ready to look at a behavioral model in the monkey" to test whether the now successful implant technique can reverse a parkinsonian-like syndrome.
But before it is tested in humans, Wyatt said, "one would like to see survival of the transplant and a change in fuction for six months to a year."
Whether experimentation in humans should even proceed based on the current, limited knowledge is controversial. Dr. Constantino Sotelo from the Centre-Medico Chirurgical Foch in Paris called for a moritorium on human experimentation until more monkey work was completed.
"We should do the monkey work first," agreed NIMH's Wyatt. "Once we have a technique worked out in the monkey, we should tell the neurosurgeons, 'Here it is. Try it.' "
But not all agreed. "We know so little that we should not close any door," said Dr. Efrain Azmitia of New York University. "If there are humans who are not doing well on drugs and they are willing to try surgery, then we should do it."
The most thorny ethical issue has yet to enter public debate: the use of human fetal brain cells, which would be collected after an abortion. Although federal laws prohibit experiments on living human fetuses, they do not forbid the use of fetal cells in research.
"As long as society feels abortion is legal and that tissue is going to die, I see no ethical reason not to use that tissue," said Dr. Roy BaKay, a neurosurgeon at Emory University, "just as there are no reasons not to use the heart or kidney for transplants from someone who bashed in his head."
"The ethical issues are rooted in the abortion issue," said Norway's Backlund. "The question is, do you believe in abortion? If you do, it would be unethical not to offer Parkinson's disease patients a chance at this operation."