In Vitro Technique Averts Family’s Sickle Cell Risk
Genetic researchers have for the first time used high-tech reproductive techniques to remove the threat of sickle cell disease from an African American family’s lineage.
Using in vitro fertilization and genetic analysis on a single cell taken from 3-day-old embryos, a team from the Weill Medical College of Cornell University helped the couple conceive healthy twin girls who were neither sufferers of the lethal disease nor carriers of the defective gene that produces it.
Although the technique has previously been used to produce children free of cystic fibrosis, Tay-Sachs disease and certain sex-linked disorders, this was the first time it had been used for such a common genetic disease, the researchers report today in the Journal of the American Medical Assn.
About 8% of American blacks carry the gene for sickle cell disease, and the incidence of the disease is about 1 in every 625 births.
Although the necessary technology has been available for nearly a decade, it has not previously been used for sickle cell disease because of the cost and technical difficulties, said Dr. Zev Rosenwaks, who led the Weill team.
Although cost will still be an issue for many families, doctors now know they can diagnose sickle cell disease in a single cell before an embryo is implanted.
“With this new capability, we can help couples who carry the genetic trait that causes sickle cell anemia, and we can virtually eliminate the risk of passing that on to their children,” Rosenwaks said. “It’s very exciting.”
That sentiment was echoed by Linda Anderson, president of the Sickle Cell Disease Assn. of America. “Any time there is an opportunity to have these kinds of breakthroughs, particularly to help those of child-bearing age make informed decisions about childbirth, I think it is miraculous.”
Anderson cautioned that the results will have to be replicated in other couples, but predicted that it could find wide use in the black community, where 90% of sickle cell cases occur.
No Cure for Disease
Sickle cell disease is caused by a small mutation in the gene that serves as a blueprint for hemoglobin, the molecule in red blood cells that carries oxygen from the lungs to other parts of the body.
Because of the mutation, the hemoglobin forms long, rod-like structures when the body is stressed, causing the red blood cells to assume a sickle shape. The sickled cells clog small blood vessels, preventing some tissues from getting enough oxygen. The condition can be quite painful, and damage to organs from the lack of oxygen can lead to severe medical problems.
Blood transfusions and a drug called hydroxyurea may alleviate some symptoms, but there is no cure for the disease. Extreme cases have been treated with bone marrow transplants, which replace the genetically defective red cells with healthy ones. That procedure has its own risks, however, and is not widely used.
Sickle cell is a recessive disease, meaning that a child must inherit a defective gene from each parent to develop the disease. People with only one copy of the defective gene are said to have sickle cell trait, a condition with few symptoms, if any.
When two adults with sickle cell trait have a child, the odds are one in four that the child will have sickle cell disease, one in two that the child will be a carrier, and one in four that the child will not inherit a defective gene.
The ability to produce the healthy babies artificially was made possible by a confluence of scientific developments. These include the ability to do in vitro fertilization, the discovery that a single cell can be removed from an early embryo without harm to the fetus, and the ability to perform genetic analysis on that single cell.
The first such success occurred in 1992 when British scientists reported the birth of the first child produced by a combination of in vitro fertilization and pre-implantation diagnosis, a little girl whose parents carried the gene for cystic fibrosis.
Today, nearly 300 children worldwide have been born after similar procedures were done to screen for a variety of genetic diseases. The in vitro diagnostic technique is also commonly used with older women, who have an increased risk of chromosomal abnormalities that can lead to miscarriages.
Rosenwaks said he and his colleagues were approached three years ago by a black couple. The woman had had two abortions because the fetuses were diagnosed with sickle cell disease by conventional amniocentesis. The couple, who wish to remain anonymous, asked the doctors if they could develop a pre-implantation diagnosis for sickle cell disease.
The Weill team developed the sickle cell analysis in conjunction with Dr. Mark Hughes of Wayne State University in Detroit and succeeded on their second attempt at in vitro fertilization. In that effort, they used sperm from the father to impregnate eggs from the mother, obtaining seven fertilized eggs.
In laboratory dishes, the eggs were then grown for three days to the blastocyst stage, in which the fertilized egg has divided into eight cells. They carefully removed a single cell from each embryo and performed genetic analysis, looking for the sickle cell gene.
Two of the embryos proved to be carriers of the gene, and one could not be diagnosed because of technical problems. These three were discarded.
Four of the embryos were found to be normal and three were implanted in the woman. Doctors generally implant several embryos during in vitro fertilization because not all will survive. In this case, two matured into fetuses and amniocentesis confirmed that they did not carry the gene.
Two healthy girls were born May 5, 1998, Rosenwaks said, and the parents were “ecstatic.”
The team has gone through one round of in vitro fertilization with another black couple, but that attempt did not result in a pregnancy, he said. In response to today’s report, Dr. Charles M. Strom of Illinois Masonic Hospital in Chicago said his team had also used pre-implantation genetic diagnosis to prevent sickle cell disease in a baby born last October.
Costly Process
The process is not cheap. In vitro fertilization costs $9,000 to $11,000 per attempt, and the genetic diagnosis can add $1,000 to $2,500 to that, he said. But the cost of raising a child with a severe genetic disease can be tens to hundreds of times that amount, he added.
Cell biologist Stuart Newman of New York Medical College, a board member of the Council for Responsible Genetics, said the procedure is acceptable because it doesn’t involve abortion or genetic manipulation of the embryo. “It’s just a more precise way of doing what they are already doing with conventional amniocentesis,” he said.
But Dr. Jon Gordon, an ethicist at Mt. Sinai Medical Center in New York City, cautioned that an incorrect genetic diagnosis in the new procedure can lead to the birth of a child with a severe defect. That happened at least once, in the early days of the technique, when a child was born with cystic fibrosis.
“It can create risks that are greater than with the standard approach” of getting pregnant and then having a genetic analysis, Gordon said. “But the great strength is that you don’t have to terminate a pregnancy.”
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Preventing a Disease
New York doctors have used high-tech reproductive techniques to produce healthy twin girls free from sickle-cell disease.
Using conventional in-vitro fertilization techniques, doctors fertilized eggs from the wife with sperm from her husband. Seven fertilized eggs were grown to a stage at which each embryo contained eight cells.
One cell was removed from each of the seven embryos and tested for the defective gene. Two of the embryos carried the defective sickle-cell gene. Based on the tests, three embryos were discarded.
Three of the four healthy embryos were implanted in the mother and two grew into fetuses.
Source: Well Medical College
