A Race for Life
Conceiving a Sibling's Perfect Match
Alexander Krzyston life Alexander J Krzyston life Alex James Krzyston
This is the story of two sick children from different families, Molly and Henry. Both Molly and Henry have an aggressive form of Fanconi anemia, which causes the bone marrow to fail, eventual leukemia and many other cancers. Fanconi children seldom live past the age of 6 years.
Alex Krzyston life Alex J Krzyston life Alexander James Krzyston
The only hope that Molly and Henry have is a genetically matched bone marrow transplant.
Many parents have conceived second children with the hope that the new baby will be a genetic match to provide a bone marrow transplant for their Fanconi sibling. The couples in the story were the first in history not to depend on luck to conceive a sibling that is a genetic match. First they used in vitro fertilization to make embryos and then use pre-implantation techniques to pick the embryo(s) with the correct genetic makeup.
Couples that conceive for the purpose of a genetic match have a test done at 10 weeks into the pregnancy find out if the fetus has the Fanconi mutation and whether the baby will be a genetic match for the sick sibling. The story tells of the heart breaking, life-altering decisions made by the two couples trying to save Molly and Henry. How to predict the likelihood of a match with the next pregnancy? "We’ll have time to try again, won’t we? He’s not that sick yet, is he?" This time Henry’s brother was not a match. They would try again.
These methods raise ethical concerns and angry rhetoric "about breeding babies for spare parts" that will lead to "breeding babies with certain hair or eye color or level of intelligence". The federal government might ban embryo research, which had made pre-implementation techniques possible. As the author says, "it is simply the story of what it now takes, in the 21st century, to save one child." p 38 NYT Magazine
Fanconi Anemia
Fanconi is a recessive genetic disorder, which means that both parents must donate one copy of the chromosome carrying the mutated gene in order for the child to inherit the disease. The mutation that causes Fanconi is most prevalent among the Ashkenazi Jews. If both parents carry the recessive mutation, the chance of having a Fanconi child is 1 in 32,000. Fanconi is a rare disease with only 800 people listed in the national registry. A well-known example of another genetic mutation that occurs at a higher rate in an ethnic sub-population is sickle cell anemia, which is most common in descendents of Africans.
This is also the story of Dr. John Wagner, University of Minnesota, who has performed more bone-marrow transplants on Fanconi children than anyone.
Pre-implantation genetic diagnosis (PGD) can be used to guarantee that the next child will be free of the genetic disease. In PGD, the egg and sperm are put together in a sterile dish. When the fertilized egg has developed into a ball of 8 cells called a blastocyst, one of the cells is carefully removed and assayed for the presence of the mutant gene. Healthy embryos are implanted in their mothers, but at this point it will be two months before they will find out if the developing embryo is a genetic match.
Dr. Mark Hughes, who worked at the prestigious National Institutes of Health (NIH), agreed to try to develop a PGD lab procedure to determine the H.L.A. type of single human blastocyst cells. This will allow him to predict whether or not the bone marrow will be a genetic match. Because Congress has banned the use of federal funds for any kind of embryo research, Dr. Hughes was forced to continue his work using only money from private sources.
The PGD procedure to find a match for Molly would be complicated by a twist in her parent’s genetic make up. To find an acceptable bone marrow donor for Molly, the doctors must match as many HLA markers as possible. Unfortunately, the HLA markers that the doctors could test at that time were close to identical in both parents, making it almost impossible to distinguish the parental genes when screening the blastocyst cells with PGD. Dr. Hughes was determined to find a way to find a match for Molly, but the case was complicated.
The headlines in the Washington Post read, "NIH Severs Ties With Researcher Who Experimented on Embryos." Dr. Hughes was accused of using federal funds to pay for his embryo work. He had to resign from NIH and Georgetown University to continue his work. He was forced to move his 2 young sons and wife who had aggressive breast cancer, to a new position at Wayne State University School of Medicine where he tried to continue his PGD embryo research.
Then Molly’s parents learned that their would not be made available to help save Molly. Dr. Hughes had analyzed their genes while at NIH and Georgetown University, and the NIH actually owned the studies involving Molly’s parents’ genetic information. Dr. Hughes appealed to Georgetown University on behalf of Molly, but was told that the Catholic administration of the hospital did not want to get involved.
Molly’s parents tried a different approach to HLA mapping with Dr. Charles Strom of Quest Diagnostics, who developed a way to distinguish the maternal and paternal HLA genes using a downstream marker. Although this approach was less effiecient, they combined it with a new in vitro fertilization clinic that had much better success rates. They also took advantage of improvements in bone marrow technology. Dr. Wagner developed a way to remove T cells from the donor bone marrow cells since T cells recognize the host as foreign and cause graft-versus-host disease. He also used an immuno-suppressant drug that "encourages" the new cells to take root in the graft. Of the 21 Fanconi patients that received transplants using the modified protocol, 13 are still alive.
Both families faced many obstacles as they attempted to conceive genetically matched siblings for Molly and Henry. It is a very difficult journey. One mother endured 353 injections and produced 198 eggs in two and a half years but did not conceive. In the end, there was no more time and Henry received a transplant from an unrelated donor. The bone marrow that Molly’s brother, Adam, gave her was a genetically chosen perfect match and Molly’s life was saved. Henry is slowly dying. His newest brother is due this fall and is genetically healthy, but unfortunately he is not a match
