Explained: 'Saviour Sibling' And Ethical Concerns About Genetic Diagnosis

One-year-old Kavya Solanki was conceived through IVF after her genes were found to match her thalassemic brother.

Six-year-old Abhijeet Solanki in Ahmedabad who earlier needed around 18-20 blood transfusions annually, is now cured of thalassemia and does not need any more transfusions, all thanks to his one-year-old sibling Kavya donating some part of her bone marrow.

Kavya Solanki is India's first-ever 'saviour sibling' who was born after her parents conducted a pre-implantation genetic diagnosis at NOVA IVF Fertility clinics. Six months after the transplantation, she is healthy and carries the minor thalassemia gene herself.

This concept of saviour siblings has started a debate on whether the procedure is ethical in itself. IVF specialists told BOOM that the pre-implantation genetic diagnosis technique is ethical and legal for single-gene diseases like thalassemia. Twitter users raised questions on whether this would set a precedent for designer babies or selecting certain babies. Questions were also raised on whether this was sex-selective.

The Solankis approached Dr. Manish Banker, Director, NOVA IVF and Dr. Deepa Trivedi, Hemato-Oncologist at Sankalp Care Institute of Medical Sciences (CIMS) hospital in Ahmedabad. According to Dr. Banker, the parents themselves were well-informed about the procedure and had approached the clinic for carrying out the technique.

The Solankis have three children. Abhijeet, the Solankis' second-born, was diagnosed with thalassemia major at birth. Their elder daughter does not carry the thalassemia gene. Till the birth of their son, the couple was unaware that both of them carried the minor gene for thalassemia. Thalassemia is an inherited genetic disorder wherein the body produces lesser hemoglobin resulting in disruption of oxygen transfer in the body.

A thalassemic major patient either needs continuous blood transfusions or a bone marrow transplant for production of newer red blood cells. Abhijeet's elder sister, however, was not a suitable match for the bone marrow transplant. Mr. Sahadev Solanki, then did his own research and came across the concept of saviour siblings and approached Dr. Banker in 2017.

Through assisted reproductive technology, several embryos were extracted and their genetic make-up was checked for features that matched with the elder sibling prior to implantation. The matching one was then implanted and the pregnancy period was completed. Kavya was born in October 2018 and the bone marrow transplantation was conducted in March 2020. Dr Banker published their case in the Journal of Human Reproductive Sciences in 2019. This mode of therapy is actively being performed in the US since 2000 (Adam Nash) and is the basis of the 2004 novel and 2009 Hollywood movie "My Sister's Keeper"

This is the first saviour sibling pair in India to have successfully completed a transplantation. Mumbai's Jaslok Hospital also witnessed the birth of another saviour sibling in 2020 whose bone marrow transplantation will occur after a year. The new-born boy will be transplanting bone marrow to his elder sister suffering from thalassemia.

Thalassemia

Thalassemia is an inherited genetic disorder wherein the body produces less hemoglobin and thus affects the transfer of oxygen in the body. Parents carrying a mutated gene could pass on the mutated gene to children during reproduction. Thalassemia can be diagnosed through a blood test called Hb Electophoresis / Hb A2.

"If both the parents carry one mutated thalassemia gene, there is a 25% chance of a child getting both the genes and being diagnosed with major thalassemia, 25% chance of them getting the normal genes and not having thalassemia, and 50% chance of them carrying one thalassemia gene," said Dr. Deepa Trivedi, Hemato-oncologist at CIMS Hospital who works with thalassemia patients.

India with over 40 million thalassemia cases witnesses around 10,000 thalassemic births every year, according to the World Health Organization. These children develop anemia as their hemoglobin production is decreased and constantly fatigued. Many children have to resort to blood transfusion and chelation therapy. The WHO further states that only 15% of the people who require blood transfusion during thalassemia can access it.

Continuous blood transfusions result in an increase in the amount of iron and ferritin in the body. These need to be removed from the body through iron chelation therapy. Drugs are administered to patients which interact with the iron in the body, break them down and remove it. Dr. Trivedi says only 39% of thalassemic people receive appropriate chelation therapy.

Several transfusions and chelation therapies lead to increased fatigue, slowed growth rate, and iron overload. Bone marrow transplants are the only way to cure thalassemia as the marrow leads to production of new oxygen-rich hemoglobin cells. Abhijeet had undergone around 80 transfusions till the time of his transplant. However, bone marrow transplants cost around 15 lakhs in the country. Sankalp Foundation at CIMS helped the family conduct the transplant in 9 lakh while the selection of the embryo and the IVF procedure cost them another 9 lakh.

Saviour Babies and Pre-Implementation Genetic Testing For Monogenic Diseases

"We selected 18 blastocysts through three rounds of ovarian stimulations and then biopsied them to match the recipient's genetic make-up. Conducting Human Leukocyte Antigen Testing we found one embryo that had the perfect chromosome number and implanted that into the mother," explained Dr. Banker.

Human Leukocyte Antigen (HLA) testing is important for any type of cell or organ transplant. These are protein markers present on cell which identify cells that are a part of the body and do not create antibodies against it. A negative HLA test wherein the body does not possess antibodies against the donated cells and organs is a precursor for conducting a transplant. At least 6 HLA markers should match between the donor and recipient. Post this, after the baby is born, their cord blood cells which are rich hematopoietic stem cells (HSC) that later grow into blood cells are transferred for a successful transplant.

Also Read:Hand Transplantations In India And Their Challenges

The embryo which had all matching markers- 10/10 was selected and implanted in Mrs. Solanki's womb. Dr. Banker added that the pre-genetic diagnosis and screening test is a well-established method for conceiving a child who may donate cord blood or HSC to save a respective sibling from a critical illness. From the 18 embryos, 2 that did not have the thalassemia mutation failed at the HLA matching stage.

The whole process takes a year - from the time the parents and affected child undergo HLA typing, to the delivery of the selected embryo. The baby was delivered through caesarean section. Her umbilical cord cells were cryopreserved as they were not sufficient for transplant. "As stem cells from the bone marrow are better accepted by the body, we waited till Kavya was of 10 kgs this March", said Dr. Trivedi. While Kavya had a fever and pain for a few days after the transplant, both of them are now healthy according to the doctors. Abhijeet has not shown any adverse reactions to the transplant.

The first saviour sibling, Adam Nash was born in the US in 2000 after HLA typing for his sister Molly who was suffering from Fanconi anaemia wherein her bone marrow barely produced any blood cells.

Ethical concerns

Saviour siblings are debated due to the ethical concerns surrounding the autonomy of the saviour sibling. While legal in US and UK, France, Italy and Germany have prohibited the procedure. A 2019 study published by Ethics professors from Heidelberg and Ulm University, Germany discussed the ethical repercussions of saviour siblings. As younger children have a higher number of HSCs, a smaller amount of their bone marrow is transplanted. They found that as far as the donor and recipient are healthy and their well-being is maintained it should not be an issue. Consent, however, becomes a major area of concern. Dr. Banker from NOVA emphasised that the process is ethical and legal.

Challenging the ethical debate that saviour siblings will only be looked at as commodities, the Nash's from America had a third child through IVF without the Fanconi gene who was not a saviour sibling.

In their 2004 paper titled "should selecting saviour siblings be banned" published in the British Medical Journal, two ethics professors from the UK highlighted the arguments against saviour siblings were skewed. They stated "the use of PGD was widely accepted for selecting babies without genetic abnormalities but the idea of saviour siblings through PGD is opposed."

Dr. Hrishikesh Pai, Director, Bloom IVF with centres at Lilavati Hospital and Fortis Hospital reiterates these findings. "Looking at the larger interest, where both the children are healthy, and the parents have consented, PGDM is ethical. The child's informed consent is an issue, yes, but it ultimately depends on the parent's choice as they are the guardians, according to the Indian law. This is very different from the sex selection technique as the country has the PC-PNDT act" said Dr. Pai. He further added that Bloom was also conducting the Pre-genetic Diagnosis tests at its Mumbai bad Delhi centres.

Prevention Better Than Cure For Thalassemia

Treatment for thalassemia is very expensive owing to the high costs linked with life-long transfusions and HSCT bone marrow transplantation. Dr. Trivedi, thus requested that couples undergo testing for thalassemia before conceiving a child. Dr. Banker added that the process of not undergoing testing could be a traumatic experience and they could conduct genetic testing for chromosomal abnormalities even in natural deliveries. IVF, and pre-implantation genetic diagnosis, then is a useful assisted reproductive technique.

This whole procedure, however, comes with its own financial constraints.

Also Read:Engagement With Fake News On Facebook Tripled Since 2016: Report


Updated On: 2020-10-16T13:12:54+05:30
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