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A savior baby,savior sibling, or donor baby is a child who is conceived in order to provide a stem cell transplant to a sibling that is affected with a fatal disease, such as cancer or Fanconi anemia, that can best be treated by hematopoietic stem cell transplantation.
The savior sibling is conceived through in vitro fertilization. Fertilized zygotes are tested for genetic compatibility (human leukocyte antigen (HLA) typing), using preimplantation genetic diagnosis (PGD), and only zygotes that are compatible with the existing child are implanted. Zygotes are also tested to make sure they are free of the original genetic disease. The procedure is controversial. [1] [2] [3]
A savior sibling may be the solution for any disease treated by hematopoietic stem cell transplantation. It is effective against genetically detectable (mostly monogenic) diseases, e.g. Fanconi anemia, [4] Diamond–Blackfan anemia [5] and β-thalassemia, in the ailing sibling, since the savior sibling can be selected to not have inherited the disease. The procedure may also be used in children with leukemia, and in such cases HLA match is the only requirement, and not exclusion of any other obvious genetic disorder.
Multiple embryos are created and preimplantation genetic diagnosis is used to detect and select ones that are free of a genetic disorder and that are also a HLA match for an existing sibling who requires a transplant. Upon birth, umbilical cord blood is taken and used for hematopoietic stem cell transplantation.
The conception of a child in order to save another raises ethical issues, the sick eldest child being doomed, unless a compatible brother or sister can treat them.
This ethical debate is reflected in the terminology used, with opponents insisting on the term "baby‐medicine" to underline the "instrumentalization of the human body". [6] For these opponents, PGD is considered "utilitarianism taken to the extreme", "human procreation is totally diverted for the benefit of the project of creating a human being whose main "mission" is to be a medicine. Project carrying a radical alienation of one's freedom since its conception is only desired because of its therapeutic potential. They have no other choice than to take on the status of reservoir of cells for their sick elder, subject to a project predetermined by others, in this case society, the medical profession and their own parents."[ citation needed ]
The Jérome Lejeune Foundation, like other religious associations, which is anti-abortion, against research on embryos, but not against assisted procreation, speaks of a "double sorting baby", because this child is the survivor of a double sorting: the 1st in relation to the disease, the 2nd, in relation to compatibility, [7] thus wanting to criticize the selection of a large number of "healthy" embryos and therefore the "interruption of the life" of future babies, and therefore a eugenic drift. Finally, these same opponents refuse the term "double hope baby", because it means the same practice as the expression "baby-medicine" – therefore the same criticisms apply.[ citation needed ]
Specialists prefer to use "child of double hope": first hope of the birth of a healthy child, second hope of curing the eldest child, "the fact of being wanted for another does not exclude being wanted at the same time." "conceiving a child in the hope that it can cure someone is not in itself immoral, provided that it is not conceived exclusively for this purpose. We can reasonably hope that parents who love their child to the point of trying everything to save him will know how to love for himself the one by whom their first child was saved."[ citation needed ]
In 2002 the National Consultative Ethics Committee (CCNE) was reserved, recalling the "risk of instrumentalization of the unborn child" and that the "selection of an embryo and the initiation of a child conceived only as a potential donor, and not primarily for himself, is not thinkable in view of the values that he has always defended." However, he puts things into perspective by indicating that "allowing a desired child to represent, moreover, a hope of recovery for his eldest, is an acceptable objective, if he is second." The Council of State questions: "The use of "double IPR" has remained exceptional (7 requests since the end of 2009). The hope offered to certain families in the face of suffering from an illness without a therapeutic solution seems not to have been fully satisfied. Therefore, it is not certain that the weight that double PGD places on the child resulting from it has found sufficient medical justification." [8]
French law rejects the concept of "medicine baby" but authorizes that of "double hope baby". [9] In 2009, the CCNE recalled its 2002 opinion "allowing a desired child to represent hope of recovery for their eldest is an acceptable objective if he is second." As the current law provides, this extreme possibility should only be reserved for couples who have a child suffering from an illness leading to death. A savior baby or savior sibling is a child who is conceived in order to provide a stem cell transplant to a sibling that is affected with a fatal disease, such as cancer or Fanconi anemia, that can best be treated by hematopoietic stem cell transplantation.
Ethical critics argue that this practice instrumentalizes these children in two ways: first, by having them for instrumental reasons rather than for their own sake, and second, by valuing them solely as a means to cure their sick sibling, potentially violating ethical principles like beneficence and nonmaleficence. Supporters, on the other hand, contend that parents' motives should not be condemned, and the key question is how saviour siblings are treated after birth. They argue that the Kantian principle prohibiting the use of individuals solely as means to an end does not apply if the saviour sibling is also treated as an end in itself. The willingness of parents to go to great lengths to conceive such a child may indicate their dedication to the welfare of all their children. [10]
Yury Verlinsky and collaborators described the first case in 2001: [14] that of Adam Nash, born 29 August 2000. [15]
Concerns regarding saviour siblings revolve around potential physical and psychological harm. Physically, there are inherent risks associated with the medical technologies involved in conceiving saviour siblings, such as in vitro fertilization (IVF), preimplantation genetic diagnosis (PGD), and hematopoietic stem cell (HSC) donation. These risks appear to be relatively low, with IVF being a routine procedure and limited short-term harm observed with PGD and HLA typing. The risks associated with HSC transplantation depend on the source of HSC and collection method, with generally low risks.
However, there is a concern about the possibility of a saviour sibling being repeatedly asked to donate HSC, which could potentially harm the child. To address this, legal safeguards can be put in place to limit the number of HSC donations by a child donor.
Psychologically, it has been suggested that saviour siblings might experience harm if they discover they were conceived primarily to be an HSC donor for their sick sibling. However, there is insufficient empirical evidence to support this claim. On the contrary, it can be argued that saviour siblings may experience psychological benefits from knowing they contributed to helping their ailing sibling, regardless of the transplantation's success. The balance between potential psychological benefits and medical risks remains a subject of debate.
Past studies on pediatric sibling donors of HSC transplantations indicate that the experience varies. In cases of unsuccessful transplantations, some siblings may experience negative emotions, particularly if the failure is linked to the sick sibling's death. Proper information, parental care, emotional support, and attention can help mitigate any potential negative psychological impacts on child donors, including saviour siblings. Overall, addressing these concerns involves careful consideration of both the physical and psychological well-being of saviour siblings during the decision-making process and throughout their lives. [16]
The novel My Sister's Keeper , later adapted into a film, is about a child who was born as a savior sibling to her sister Kate who is affected by acute promyelocytic leukemia.
In the British soap opera Emmerdale , Debbie Dingle gave birth to her son Jack, who would serve as a savior sibling to his older sister Sarah, who was suffering from Fanconi anemia.
On the popular American show CSI: Crime Scene Investigation , the episode "Harvest" deals with the reported abduction and later murder of a thirteen-year-old girl named Alycia who was later revealed to be a savior sibling for her brother Daniel.
In the American show Heroes , one of the protagonists, Mohinder Suresh, is revealed to have been conceived to cure his sister Shanti of a deadly disease known as the Shanti Virus, although he was ultimately born too late to save her life. His antibodies act as a cure for other patients with the disease throughout the show as well.
On Star Trek: Enterprise , the episode "Similitude" sees a clone created of Trip Tucker for the purpose of organ harvesting. "Sim" is born through the highly controversial use of an alien lifeform.
The novel Never Let Me Go , later adapted into a film, is centred around a dystopian future society where human clones are created and allowed to live to their teenage years before being used for organ harvesting. The film Parts: The Clonus Horror has a similar premise.
In the Grey's Anatomy episode "I Bet It Stung," the character Donna is a savior sibling to her older sister Reese.
In the 9-1-1 episode "Buck Begins", it is revealed that Evan "Buck" Buckley was conceived as a savior sibling for his older brother Daniel.
In the Korean drama The Penthouse , the character Anna is adopted by a Korean-American family to be a savior sibling to their son, Logan Lee, who was suffering from bone marrow cancer at the time.
Aplastic anemia (AA) is a severe hematologic condition in which the body fails to make blood cells in sufficient numbers. Blood cells are produced in the bone marrow by stem cells that reside there. Aplastic anemia causes a deficiency of all blood cell types: red blood cells, white blood cells, and platelets.
Thalassemias are inherited blood disorders that result in abnormal hemoglobin. Symptoms depend on the type of thalassemia and can vary from none to severe. Often there is mild to severe anemia as thalassemia can affect the production of red blood cells and also affect how long the red blood cells live. Symptoms of anemia include feeling tired and having pale skin. Other symptoms of thalassemia include bone problems, an enlarged spleen, yellowish skin, pulmonary hypertension, and dark urine. Slow growth may occur in children. Symptoms and presentations of thalassemia can change over time. Older terms included Cooley's anemia and Mediterranean anemia for beta-thalassemia. These have been superseded by the terms Transfusion-Dependent Thalassemia (TDT) and non-Transfusion-Dependent Thalassemia (NTDT). Patients with TDT require regular transfusions, typically every two to five weeks. TDTs include Beta-thalassemia major, nondeletional HbH disease, survived Hb Bart's disease, and severe HbE/beta-thalassemia.
The human leukocyte antigen (HLA) system or complex of genes on chromosome 6 in humans which encode cell-surface proteins responsible for regulation of the immune system. The HLA system is also known as the human version of the major histocompatibility complex (MHC) found in many animals.
Fanconi anemia (FA) is a rare, autosomal recessive, genetic disease resulting in impaired response to DNA damage in the FA/BRCA pathway. Although it is a very rare disorder, study of this and other bone marrow failure syndromes has improved scientific understanding of the mechanisms of normal bone marrow function and development of cancer. Among those affected, the majority develop cancer, most often acute myelogenous leukemia (AML), MDS, and liver tumors. 90% develop aplastic anemia by age 40. About 60–75% have congenital defects, commonly short stature, abnormalities of the skin, arms, head, eyes, kidneys, and ears, and developmental disabilities. Around 75% have some form of endocrine problem, with varying degrees of severity. 60% of FA is FANC-A, 16q24.3, which has later onset bone marrow failure.
Preimplantation genetic diagnosis is the genetic profiling of embryos prior to implantation, and sometimes even of oocytes prior to fertilization. PGD is considered in a similar fashion to prenatal diagnosis. When used to screen for a specific genetic disease, its main advantage is that it avoids selective abortion, as the method makes it highly likely that the baby will be free of the disease under consideration. PGD thus is an adjunct to assisted reproductive technology, and requires in vitro fertilization (IVF) to obtain oocytes or embryos for evaluation. Embryos are generally obtained through blastomere or blastocyst biopsy. The latter technique has proved to be less deleterious for the embryo, therefore it is advisable to perform the biopsy around day 5 or 6 of development.
Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood, in order to replicate inside a patient and produce additional normal blood cells. HSCT may be autologous, syngeneic, or allogeneic.
Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants.
A cord blood bank is a facility which stores umbilical cord blood for future use. Both private and public cord blood banks have developed in response to the potential for cord blood in treating diseases of the blood and immune systems. Public cord blood banks accept donations to be used for anyone in need, and as such function like public blood banks. Traditionally, public cord blood banking has been more widely accepted by the medical community. Private cord blood banks store cord blood solely for potential use by the donor or donor's family. Private banks typically charge around $2,000 for the collection and around $200 a year for storage.
A designer baby is a baby whose genetic makeup has been selected or altered, often to exclude a particular gene or to remove genes associated with disease. This process usually involves analysing a wide range of human embryos to identify genes associated with particular diseases and characteristics, and selecting embryos that have the desired genetic makeup; a process known as preimplantation genetic diagnosis. Screening for single genes is commonly practiced, and polygenic screening is offered by a few companies. Other methods by which a baby's genetic information can be altered involve directly editing the genome before birth, which is not routinely performed and only one instance of this is known to have occurred as of 2019, where Chinese twins Lulu and Nana were edited as embryos, causing widespread criticism.
Cord blood is blood that remains in the placenta and in the attached umbilical cord after childbirth. Cord blood is collected because it contains stem cells, which can be used to treat hematopoietic and genetic disorders such as cancer.
Preimplantation genetic haplotyping (PGH) is a clinical method of preimplantation genetic diagnosis (PGD) used to determine the presence of single gene disorders in offspring. PGH provides a more feasible method of gene location than whole-genome association experiments, which are expensive and time-consuming.
The National Marrow Donor Program (NMDP) is a nonprofit organization founded in 1987 and based in Minneapolis, Minnesota, that operates the Be The Match Registry of volunteer hematopoietic cell donors and umbilical cord blood units in the United States.
Yury Verlinsky was a Russian-American medical researcher specializing in embryonic and cellular genetics. He is best known as a pioneer in prenatal diagnosis for detecting genetic and chromosomal disorders six weeks earlier than standard amniocentesis. The founding father of pre-implantation genetic diagnosis (PGD) and embryo analysis prior to in-vitro fertilization (IVF), Verlinsky used his polar body biopsy technique to detect potential birth defects in offspring. It is now accepted worldwide as the standard for the most efficient and effective means of analyzing the chromosomal status of an embryo.
Laurie Strongin is an American author and medical research campaigner.
Bone marrow failure occurs in individuals who produce an insufficient amount of red blood cells, white blood cells or platelets. Red blood cells transport oxygen to be distributed throughout the body's tissue. White blood cells fight off infections that enter the body. Bone marrow progenitor cells known as megakaryocytes produce platelets, which trigger clotting, and thus help stop the blood flow when a wound occurs.
Reticular dysgenesis (RD) is a rare, inherited autosomal recessive disease that results in immunodeficiency. Individuals with RD have mutations in both copies of the AK2 gene. Mutations in this gene lead to absence of AK2 protein. AK2 protein allows hematopoietic stem cells to differentiate and proliferate. Hematopoietic stem cells give rise to blood cells.
Adam Nash is an American who was conceived using preimplantation genetic diagnosis (PGD).
Graft-versus-tumor effect (GvT) appears after allogeneic hematopoietic stem cell transplantation (HSCT). The graft contains donor T cells that can be beneficial for the recipient by eliminating residual malignant cells. GvT might develop after recognizing tumor-specific or recipient-specific alloantigens. It could lead to remission or immune control of hematologic malignancies. This effect applies in myeloma and lymphoid leukemias, lymphoma, multiple myeloma and possibly breast cancer. It is closely linked with graft-versus-host disease (GvHD), as the underlying principle of alloimmunity is the same. CD4+CD25+ regulatory T cells (Treg) can be used to suppress GvHD without loss of beneficial GvT effect. The biology of GvT response is still not fully understood but it is probable that the reaction with polymorphic minor histocompatibility antigens expressed either specifically on hematopoietic cells or more widely on a number of tissue cells or tumor-associated antigens is involved. This response is mediated largely by cytotoxic T lymphocytes (CTL) but it can be employed by natural killers as separate effectors, particularly in T-cell-depleted HLA-haploidentical HSCT.
Guo Mei is a hematologist and associate director of 307th Hospital of Chinese People’s Liberation Army and deputy director of Radiation Research Institute.
Intersex people are born with natural variations in physical and sex characteristics including those of the chromosomes, gonads, sex hormones, or genitals that, according to the UN Office of the High Commissioner for Human Rights, "do not fit the typical definitions for male or female bodies". Such variations may involve genital ambiguity, and combinations of chromosomal genotype and sexual phenotype other than XY-male and XX-female. Preimplantation genetic diagnosis allows the elimination of embryos and fetuses with intersex traits and thus has an impact on discrimination against intersex people.