MEDICINE FETAL-TO-FETAL TISSUE TRANSPLANT : Physicians, Parents Test Boundaries of Medical Knowledge
The first fetal-to-fetal tissue transplant in the United States demonstrates how physicians and parents are willing to test the boundaries of medical knowledge in an attempt to cure fatal childhood diseases.
The deceptively simple experimental procedure was performed in May, 1990, by Dr. R. Nathan Slotnick of the UC Davis School of Medicine who said this week he was “still in limbo” about whether it was successful. The transplant was not announced publicly until Monday in Washington, as a House subcommittee considered legislation that would overturn a ban on federal funding for fetal tissue research.
The 5-month-old boy, Nathan Walden of Houston, has Hurler’s syndrome, a rare, inherited condition. In the syndrome, a missing enzyme causes excessive amounts of a special type of carbohydrate, known as a mucopolysaccharide, to accumulate in the body. The buildup of the material leads to brain, heart, liver and skeletal abnormalities and death by age 10.
The case opens up a new area for American medicine and touches on matters of ethics and conscience.
Many parents at risk of giving birth to a Hurler’s baby will choose an abortion after the diagnosis is confirmed by prenatal tests. But others, such as Guy and Terri Walden, are opposed to abortion.
“The real motivation for this is to provide options for couples that are more than abortion or allowing the pregnancy to go untreated,” Slotnick said. “There have been sophisticated fetal diagnostic tests for years, but there are relatively few therapies when life-threatening diseases are found.”
But fetal-to-fetal tissue transplants for diseases such as Hurler’s remain “scientifically very controversial,” said Arthur Caplan, the director of the Center for Biomedical Ethics at the University of Minnesota.
The major uncertainties are whether the transplant will take, and even if it does, whether it can prevent the ravages of disease, particularly the brain damage.
“It is a nice idea. The question is does it work?” said Dr. Joseph Muenzer, a specialist in childhood metabolic diseases at the University of Michigan Medical Center in Ann Arbor. “Even though children (with the disease) are born looking normal, they clearly already have damage that has occurred.”
Fetal-to-fetal tissue transplants have been attempted about 10 times with no better than inconclusive evidence of success, according to experts in the field. Some of the recipients had diseases related to Hurler’s, others had blood cell disorders. There also have been about 150 bone marrow transplants for childhood metabolic diseases with varying degrees of success.
The skills needed to perform the fetal cell transplant are similar to those for amniocentesis, a prenatal diagnostic test in which a sample of the fluid that surrounds the fetus is withdrawn from the womb under the guidance of an ultrasound machine.
The procedure has to be done carefully to avoid killing the fetus, causing a miscarriage or injuring the mother’s uterus.
Doctors hope that the transplanted cells will migrate to the bone marrow and produce normal blood cells that contain the vital enzyme which is missing from the recipient’s own cells. The transplant should not affect the recipient’s own cells, which should continue to grow and develop.
In the procedure, immature cells that develop into bone marrow cells were isolated from a fetal liver. The tissue was donated by a woman with a 13-week pregnancy that had to be terminated because it had developed outside the womb.
About half a teaspoon of a solution of purified cells was injected into the abdomen of a 15-week-old fetus as it developed in its mother’s womb.
A fetal-to-fetal tissue transplant seems attractive for several reasons, according to Slotnick and other experts in the field.
First, it might prevent damage caused by the missing enzyme before the child is born.
Second, the transplant itself might cause fewer problems than a bone marrow transplant performed after birth. In a fetal-to-fetal tissue transplant, both the transplanted cells and the immune system of the recipient are still immature.
This minimizes the possibility of severe immunologic reactions, which could doom the transplant to failure. The recipient’s own bone marrow does not need to be destroyed, as is the case in a bone marrow transplant.
The UC Davis experiment is the culmination of many years of research. At the University of Nevada School of Medicine in Reno, Esmail D. Zanjani developed the techniques to isolate the blood-forming cells from fetal liver.
During a fellowship at UC San Francisco, Slotnick began tests in monkeys on the feasibility of performing fetal liver transplants in the womb.
Since 1987, the research group has performed nearly 20 transplants in monkeys. After “ironing out procedural complications,” Slotnick said, most of the transplants had been successful.
The monkeys have grown normally and remained healthy for several years. Both types of bone marrow cells produce blood cells and do not interfere with each other.
Slotnick learned that the transplants had to be performed early in pregnancy--no later than 80 to 100 days into a monkey’s 165-day pregnancy. After that time, the recipient monkey’s immune system was sufficiently developed to reject the transplanted cells.
But a key difference is that the tests have been performed with otherwise healthy monkeys, not in monkeys with a disease similar to Hurler’s syndrome.
Within the next four to six weeks, Slotnick hopes to have the results of laboratory tests that will show whether Nathan Walden’s transplant worked. If unsuccessful, he is expected to undergo a bone marrow transplant.
Slotnick hopes to perform additional fetal transplants. Each case will be reviewed individually by a team of UC Davis officials.
“I would like to have rigorous standards established for fetal therapy,” he said. “I am very much troubled that poorly conceived or poorly executed research could harm both the scientific endeavor and the patients who are treated.”
FETAL-TO-FETAL TISSUE TRANSPLANT In the experimental procedure, immature cells that develop into bone marrow cells were taken from the liver of an aborted fetus and purified in the laboratory.
About half a teaspoon of a solution of the purified cells was then injected, using a needle and a syringe, into the abdomen of the 15-week-old fetus in the mother’s womb.
The hope is that the transplanted cells have migrated to the bone marrow and started to produce normal blood cells that contain a vital enzyme missing from the recipient’s own cells.
The procedure, performed by Dr. R. Nathan Slotnick of the UC Davis School of Medicine, was the first of its kind in the United States.
