Steps Toward a Brave New World

By LEON JAROFF

For more than a year, Tess Follensbee had found it easier to start moving her rigid muscles if she walked backward, so pronounced was her Parkinson's disease. In May, all that changed. The 39-year-old mother of four was one of the first half a dozen Americans to undergo experimental brain surgery for Parkinson's at Vanderbilt University Medical Center in Nashville. Last week some 500 medical researchers, gathered at a symposium sponsored by the University of Rochester in New York, watched a videotape of Follensbee in awed silence as she triumphantly, if tentatively, propelled herself forward. Says the patient, who still suffers from slight tremors: "I have hope where there was no hope before."

The surgery that preceded Follensbee's partial recovery -- the transplanting of tissue from one of her adrenal glands to her brain -- may be only a prelude to even more remarkable developments. Several scientists at the Rochester meeting, citing promising research on animals, predicted that human fetal tissue would eventually be implanted in brains not only to treat Parkinson's but Huntington's and Alzheimer's diseases as well as other brain disorders. Given the rapid surgical advances recently, there is no question that the rush is on to try adrenal-cell implants to correct Parkinson's, a neural disorder that afflicts an estimated 1 million Americans. At the Rochester conference, doctors from China to Mexico reported successes in dozens of adrenal implants. At least four U.S. medical centers, including New York University in Manhattan and Rush-Presbyterian-St. Luke's in Chicago, are planning to perform the operation on at least 30 Parkinson's victims in the next six months.

Parkinson's disease, which causes trembling and muscular rigidity, stems from the still unexplained gradual death of most of the cells in a tiny, darkly pigmented area of the brain called the substantia nigra. The cells produce dopamine, a chemical that helps transmit impulses from the brain through the nervous system to the muscles. The Vanderbilt operations, adapting a technique that was developed in Sweden and first used successfully in Mexico last year, involve transplanting dopamine-producing tissue from one of the patient's two adrenal glands (located atop the kidneys) into the brain. Since the cells are the patient's own, there is no danger of rejection by the immune system. They are accepted by the brain and begin producing the needed dopamine.

Despite the heartening Parkinson's results reported in Rochester, doctors at the symposium were cautious. "In my mind, there is no question that the patients get better," said Dr. Rene Drucker-Colin, a leader of the transplant team at Universidad Nacional Autonoma de Mexico, in Mexico City. "The real question is: For how long will they get better? Obviously, if the answer is six months, it would be less important to do this operation." Admitted Dr. George Allen, chairman of the department of neurosurgery at Vanderbilt, where twelve more operations are planned later this year: "This is still very much an experimental procedure. It is too early to tell if the improvement is due to the operation."

Whether or not the recoveries prove to be long lasting, University of Rochester Neurobiologist John Sladek and Yale Psychiatrist Eugene Redmond see a braver new world ahead. The two scientists reported reversing the effects of Parkinson's in adult African green monkeys by implanting cells from the substantia nigra of monkey fetuses, and believe that fetal brain grafts offer a better bet for Parkinson's patients. Vanderbilt researchers, using fetal nerve-tissue implants in experiments with rats, also reported progress in reducing chemically induced symptoms of Huntington's disease, a fatal genetic brain disorder. Others expressed hope that once the underlying causes of Alzheimer's disease are determined, it too might be brought under control by implants of fetal tissue.

Despite some optimistic statements, most scientists are aware that ethical dilemmas as well as technical difficulties stand in the way of successful fetal-cell therapy. Many church leaders and right-to-life advocates oppose the use of tissue from artificially aborted fetuses. And doctors worry about using tissue from spontaneously aborted fetuses, which often have serious genetic defects. In any event, Sladek believes animal research on fetal tissue should continue for several more years before fetal-cell transplants are even attempted in humans. He and Redmond plan to treat monkeys and observe them for two to five years in order to detect any unexpected long-range effects. Still, Sladek is optimistic. Says he: "I just know it's going to work."

Another Rochester neuroscientist, Timothy Collier, has already begun looking into freezing and storing fetal brain tissue for use in implants. He reported last week that he had successfully transplanted frozen-and-revived fetal neural tissue in both rats and monkeys. The next step: implanting the thawed tissue into monkeys afflicted with Parkinson's. The ultimate aim is to create neural-tissue banks that surgeons will be able to draw on for future operations.

Animal research may help answer some basic physiological questions about fetal brain implants. Will the brains of Parkinson's victims, most of whom are middle-aged or elderly, integrate with fetal tissue? Could a virus that found its way into the brain, which is normally unaffected by the immune system, accidentally set off an abnormal immune response that would destroy the graft? And even without viral intervention, would the foreign fetal cells be rejected? Moreover, surgeons will have to know precisely how much tissue from what stage of development should be used in each transplant. Taking the tissue too early, for example, might result in runaway cell growth that could wreak havoc in the brain.

Sladek, for his part, believes that technology may circumvent some of these dilemmas. "We may someday be able to genetically engineer the cells we need -- add the genes for dopamine to cells, grow them in culture and use them in the brain. Whatever happens," he says, "it will be exciting." Notes New York University Neurologist Abraham Lieberman, who will assist in N.Y.U.'s first adrenal-cell transplant this week: "Five years ago, when you talked about brain transplantation, you were talking about Boris Karloff and Frankenstein. Today it's no longer science fiction."

With reporting by Andrea Dorfman/Rochester and Christine Gorman/New York