Cures From The Womb

The abortion took only seven minutes, punctuated by the tinkle of stainless-steel instruments, then the gurgle of the suction as it carried the embryo and placenta down a tube snaking through a hole in the wall. On the other side a nurse carrying a small plastic dish collected the remains of the six-week embryo, all two ounces' worth. But this one wasn't going to the incinerator. A technician raced the tissue to a sterile table, whittled out a few grams of neural cells and put them on ice. Other scientists performed rapid-fire tests: No genetic defects. No AIDS. No bacterial contamination. Six hours later the tissue was rushed upstairs to the hospital operating theater where surgeons drilled a hole the size of a thimble into the skull of a Parkinson's patient. The surgeon pulled the fetal cells into a tiny needle and, using an MRI scan to pinpoint the area crippled by the incurable disease, shot them into the brain of the awake and alert patient.

What happened in that hospital? A life was ended and a life was saved. Or, an unborn child was killed, and a desperate, dying man underwent an experimental operation unlikely to help him.

It is the Rashomon of science. There are as many ways to describe the use of tissues from aborted fetuses as there are individual values through which the practice is refracted. On his third day in office, President Bill Clinton rescinded the Reagan-era ban on spending federal funds for the transplantation of tissue from aborted fetuses into humans. His goal, Clinton said, was to "free science and medicine from the grasp of [abortion) polities." Maybe he succeeded: the right-to-life movement didn't offer any irate denunciations. But scientists, long frustrated at being held hostage to political debate, were ecstatic. "For years this field has practically stood still," says Dr. Gary Hodgen, a fetal researcher at Eastern Virginia Medical College who left the National Institutes of Health (NIH because of government restrictions on research. "It's the greatest day for science since the Scopes monkey trial."

Scopes, of course, was convicted. Rather than ending the debate, Clinton may have only brought it to a boil. Two weeks ago Congress held hearings addressing the regulation of fetal-tissue research. The questions did not lend themselves to sound bites. May a child be conceived with the express purpose of aborting it in order to donate its cells to an ailing relative? Should a woman weighing an abortion be told that her fetus might save another child? Can doctors change their abortion procedures in order to get more usable fetal tissue?

Donna Shalala, secretary of health and human services, promised Congress quick regulations on all these issues. She said HHS would make sure that the new frontier of fetal research and therapy did not become an excuse to encourage more abortions or cheapen fetal life. But HHS was playing catch-up. The ban, which President Reagan decreed in 1988 as part of his anti-abortion policies, affected only the use of federal money for the transplantation of tissues obtained by elective abortion, of which there were 1.6 million last year. Fetuses aborted spontaneously, or from ectopic pregnancies (in which the fetus grows in a fallopian tube rather than the uterus and can kill the mother), were fair game. So was pure research, using fetal tissue to study fundamental scientific puzzles. Thanks to such exceptions, a handful of researchers have been performing both clinical and basic experiments throughout the ban. Using private money for transplants and close to 5 million from NIH for scientific work, they have been trying to treat Parkinson's disease and diabetes, fathom the mystery of how embryonic cells decide whether to turn into heart or skin, and untangle the secrets of the nascent brain. The removal of the stigma that the ban caused means fetal-tissue research will multiply. And the prospect of more experiments has only sharpened the ethics debate over this brave new field (page 53).

In theory, fetal cells are perfect for a host of scientific and medical uses. The cells grow quickly and divide rapidly, and so are more likely to insinuate themselves into a patient's existing tissue. They lack the surface markers that a recipient's immune system recognizes as foreign, and so are unlikely to be rejected. Perhaps most important, they are "plastic": a very young fetal cell has the potential to be a kidney, a liver cell or just about anything else. Studying the genetic switches that determine the road not taken can yield insights into why some fetuses do not develop properly. And under the right circumstances (which researchers haven't figured out yet), science might one day grow a full, functioning kidney from a few fetal kidney cells.

In 1928, surgeons in Italy became the first to exploit these properties. They transplanted pancreatic tissue from three fetuses into a patient with diabetes. The patient did not get better. In 1939, physicians in the United States tried the operation, twice, also without success. In 1959 another American researcher tried to cure a leukemia patient with transplanted fetal cells; there was no lasting improvement. Scientists had better luck with vaccines: immunizations for polio, rubella and Rh disease were all developed using fetal kidney and other cells. The first glimpse of success with transplants came in 1968, when fetal liver cells were grafted into patients suffering DiGeorge syndrome, a rare and usually fatal genetic disorder marked by multiple abnormalities of glands and organs, including the heart. DiGeorge's, which strikes one in 10,000 newborns, became the only condition for which fetal-tissue transplants were accepted treatment.

Today the most tantalizing target for fetal-tissue therapy is Parkinson's disease. More than 500,000 Americans suffer from this disorder, in which the motor-control area of the brain does not receive a steady supply of the neurotransmitter dopamine from a region of the brain stem that the disease somehow has wiped out. Patients cannot control their movements; they suffer tremors, rigidity and eventually paralysis. Drugs that stimulate brain cells to produce dopamine have horrible side effects, including psychosis, and become less and less effective over time. So researchers, after years of animal experiments, hit on the idea of implanting into the brains of Parkinson's patients a permanent source of dopamine. That source was neural cells from fetuses.

In 1988, Dr. Curt Freed of the University of Colorado Health Sciences Center performed America's first fetal-cell transplant into a Parkinson's patient. Don Nelson, 52, was so far gone he could barely walk. Today he has returned to his beloved woodworking and is taking less medication-mainly the dopamine-boosting drug, L-dopa-than before the transplant.

Other cases range from the ambiguous to the miraculous. Freed has reported on six more patients: none is completely cured, but they're all taking less medication and one, who could neither speak nor drive, now does both. At the Yale School of Medicine, Dr. Eugene Redmond has done 13 similar operations; in the first group, three of the four patients improved somewhat. A Swedish team led by Anders Bjorklund and Olle Lindvall of the University of Lund, who in 1987 first reported that fetal cells remain alive and pump out dopamine in the recipient's brain, announced in December that brain-stem tissue from 6- to 8-week-old fetuses blossoms into fully functioning cells that substitute for the missing dopamine cells. "It brings patients back [to where they were] five to seven years" earlier, says Bjorklund.

For all the promise, though, the verdict is still out on the success of fetal transplants for Parkinson's. In a sort of "why throw good cells after bad" logic, opponents of fetal transplants claim that the less than clear-cut results argue against more widespread testing of the procedure. But as Bjorklund points out, "What is needed [to determine the efficacy of the surgery] is very controlled clinical trials in a well-designed scientific framework. This is what is vitally important about the lifting of the moratorium in the U.S."

Clinton's action has also renewed hope among other patients whose otherwise incurable diseases might one day be treated with fetal transplants. Among them:

Other neurological disorders are also candidates for fetal grafts. In Alzheimer's disease, for instance, the nerve cells in the brain begin churning out the neural equivalent of arterial plaque: the substance cripples neurons' ability to communicate, eventually killing nerve cells outright and robbing patients of their memories, their abilities, their very lives. Alzheimer's will be a challenge for transplant surgeons, however, because neuronal death is so widespread it's hard to see where cells could be implanted. It's more obvious that transplants might one day repair spinal-cord damage, which 180,000 Americans suffer from every year: neural cells grafted into animals make the damaged neural fibers grow back. Neural transplants might also cure victims of myelin diseases, such as ALD, made famous by the film "Lorenzo's Oil." Lorenzo's father, Augusto Odone, has set up a foundation to research myelin diseases; he says the first transplants of human fetal cells into an ALD victim may be carried out this year. Before last month he figured that would happen in Europe. Now it may take place in the United States.

There are at least 155 other genetic disorders, including sickle cell anemia, thalassemia, metabolic disorders and immune deficiencies, that could be corrected before birth with fetal tissue. "The potential is quite fabulous," says Dr. Michael Harrison of UC, San Francisco. "Fetuses have a whole variety of problems that can be cured for their lifetime with in utero transplants."

Although using fetal tissue to treat disease is the splashiest application, the cells are also being used for more basic research. And for a lot of it: for three decades a program at the University of Washington has collected more than 10,000 fetuses through private clinics and distributed them to some 60 research labs nationwide. Reagan's ban did not affect these scientific experiments, but they, too, have nevertheless been engulfed by abortion politics. Some scientists contacted by NEWSWEEK did not want to discuss their work for a story that also described previously banned fetal-tissue work, for fear of being targeted by anti-abortion protesters.

A pioneer in fetal transplants for basic science is J. Michael McCune, research director of a Palo Alto company called Systemix. In 1990 he transplanted tiny pieces of thymus, liver and lymph from human fetuses into mice born with no immune system. Within two months the transplants had grown to the size of a peanut and were producing human immune cells. Now the mouse has become a unique animal model for AIDS (the AIDS virus does not infect nonhuman tissue) and is used to screen possible AIDS treatments. Last year the mouse also helped Systemix isolate the crucial precursor cell that differentiates into all the varied cells of the human blood system. That may help scientists understand how the blood and immune systems develop, and how they go awry.

The brain, too, begins life with cells that aren't sure what they want to be when they grow up. In the intricate choreography that is an embryo's development, there is no more complex, or baffling, dance than the one that turns a few wisps of neurons into a brain that can see, think, love and ponder its own existence. The only way to find out how this happens is by studying embryonic neural cells before they have cast their lot with, say, the motor-control center or the visual cortex. At the Massachusetts Institute of Technolology, Ron McKay has found a gene that keeps neural cells from differentiating: as long as the gene is working, the cells retain their limitless potential. He's interested in finding "what all these genes do in the brain." If he can understand how a neural cell in a fetus finds its destiny, "it will provide a deeper understanding of the biochemistry that underlies diseases" such as schizophrenia.

Cells of the brain differ from those of the skin in not being able to repair themselves. That's why strokes are forever, but scraped knees aren't. At UC, San Diego, Fred Gage is studying fetal neural cells to understand how they mature into discrete types and, even more wondrous, migrate to precisely the right spot in the brain where all the other language neurons, for instance, are gathering. By growing fetal cells to identify what makes them differentiate and migrate, Gage and others have identified brain chemicals that affect neural survival and growth. "It's a revolution," he says. "Now molecules are available to attempt real brain repair and surgery." That's been tried in animals; people may get their turn in a few years.

Science has a way of defusing incendiary issues through breakthroughs that make the controversial anachronistic. Just two years ago it looked as if endangered Pacific yew trees would have to be harvested in order to extract a compound, Taxol, that shows promise against ovarian and breast cancer. But now there's another source of Taxol. A similar fate may await fetal-tissue research. "If we can use cells [grown in the lab] to accomplish the same goals," says bioethicist Dorothy Vawter of the University of Minnesota, fetal tissue may turn out to be just a "temporary solution." In fact, at least two researchers are perfecting ways to grow dozens of cell types for unlimited generations. If they succeed, it will be no more necessary to obtain fast-growing, rejection-resistant tissue from fetuses than it is to get sponges from the ocean. And the value of fetal-tissue research and therapy can finally be assessed on its merits, free at last from the distorting cloud of abortion politics.

Fetal tissue is fast growing, adaptable and unlikely to be refected by a patient's immune system. Some possible uses:

In experimental surgery, studies reported that 10 out of 13 patients improved when brain cells from 6- to 11-week-old fetuses were implanted in the affected part of their brain.

Neurons from 8- to 14-week-old fetuses might treat spinalcord injuries and multiple sclerosis. Transplant for ALD, "Lorenzo's disease," possible in 1993.

Insulin-making pancreas cells from 10- to 20-week-old fetuses reduced patients' need for insulin.

Liver cells from a 13-week-old fetus helped one boy with this rare enzymatic disorder; highly experimental.

Stem cells from fetuses ounger than 16 weeks might treat sickle cell anemia, thalassemias, aplastic anemia and other disorders.

Cures From The Womb | News