SINGAPORE: The Bioethics Advisory Committee (BAC) is reviewing its current stand against genetic modification with regards to genetic disorders passed on to children by their mothers.
The committee, set up by the Government to deal with issues arising from biomedical sciences research in Singapore, said on Thursday (Apr 19) that it is seeking public feedback and views on whether emerging technology should be allowed to be used to prevent mitochondrial disorders.
Mitochondria are responsible for energy production in cells, and faulty mitochondria can have “serious debilitating effects”, including brain, heart and ear disorders, the committee said.
A public consultation paper put up by the committee - which includes retired chief district judge Richard Magnus, chief executive of Science Centre Singapore Lim Tit Meng and senior consultant at the National Cancer Centre Singapore Professor Kon Oi Lian - looks at the ethical, legal and social issues arising from Mitochondrial Genome Replacement Technology (MGRT).
MGRT, which involves germline modification, a type of genetic modification, has so far not been permitted in Singapore. The BAC recommended against it in 2005 due to the lack of sufficient scientific evidence of its feasibility and safety.
However, “in light of recent scientific developments and international debates” the committee is reviewing its position, it said in its paper.
A spokesperson for the BAC pointed to the United Kingdom, which became the first country to legalise the clinical application of MGRT in 2015, allowing clinical trials for two MGRT techniques, as an example of such developments.
With these developments, the BAC considers it “timely and important” to study the current research involving MGRT, and to review its recommendations, he added.
The three techniques the committee is looking at involve replacing the abnormal mitochondria in the egg or early embryo with healthy mitochondria from the egg or early embryo of a separate healthy donor. Fathers are not able to pass on such disorders.
BAC chairman Mr Magnus said: “MGRT may help enable women who suffer from mitochondrial disorders to have healthy genetically related children of their own.
"However, there is a need to closely evaluate the safety of MGRT and the resulting ethical, legal and social implications, and consider if Singapore is ready to permit such technology.”
HOW COMMON ARE MITROCHRONDIAL DISORDERS AND IS THERE A CURE?
According to the consultation paper, the prevalence of heritable mitochondrial diseases in Singapore has not been studied.
However, as there is “no significant racial or ethnic predilection for mitochondrial diseases”, it is likely that population studies done in other countries can be extrapolated to Singapore, the paper said.
In the United Kingdom, it has been estimated that approximately 1 in 4,300 people suffer from inheritable mitochondrial disease, of which the minimum prevalence rate for mitochondrial disease caused by mitochondrial DNA mutations is 1 in 5,000.
“However, because of the wide range and varying severity of symptoms, it is thought that the prevalence of mitochondrial disorders is likely to be higher than current estimates mainly due to a lack of recognition leading to under-diagnosis or misdiagnosis,” the paper said.
The paper added that there is currently no cure for mitochondrial disorders, though many symptoms are treatable.
Existing treatments include transplantation, medication, and special diets. However, these treatments vary in efficacy.
The paper added that the risk of transmitting mitochondrial disorders due to mitochondrial DNA mutations can be complex and difficult to predict.
Currently, women carrying abnormal mitochondrial DNA who wish to have healthy children without the risk of developing mitochondrial disease may consider adoption, in-vitro fertilisation using healthy donor eggs, preimplantation genetic diagnosis and prenatal diagnosis, the paper said.
However, it added that these solutions come with difficulties and limitations like a long waiting list for adoption.
POTENTIAL BENEFITS AND HARMS OF USING SUCH TECHNOLOGY
The key benefit of MGRT is the potential elimination of mitochondrial disorders caused by mitochondrial DNA mutation and the avoidance of physical, psychological or social suffering associated with the disorders, according to the committee.
“MGRT offers an opportunity to mitigate the undesirable outcomes of the 'genetic lottery', so that affected individuals could have children potentially unaffected by mitochondrial disorders,” the paper said.
This prevents suffering not only for their future children, but also for the prospective parents, the paper added.
However, the paper acknowledged that it would be difficult to assess the potential harm from the clinical application of MGRT because human trials have not yet been conducted.
Nevertheless, the paper addressed some foreseeable harm to future generations, such as a possible developmental or health problems due to the manipulation of the eggs or zygotes.
Another is psychosocial harm.
“It has been suggested that children, if informed that they were born via MGRT and possess genetic material from three different persons, may form a self-conception that is troubling, ambiguous or conflicted,” the paper said.
The current challenge lies in determining what an ethically acceptable threshold of risk versus benefits should be, in comparison with the available alternatives in order for first-in-human trials to proceed, the paper said.
In suggesting safeguards for the use of the technology, the committee suggested enhancing current regulation to limit the use of MGRT to the prevention of serious mitochondrial disease, an approach adopted similarly in the UK.
Professor Kon, chairman of the MGRT Review Group, said that while introducing inheritable genetic changes carries unforeseeable risks, current pre-clinical scientific evidence suggests that MGRT is not unsafe.
“Due to the unique characteristics of mitochondria, there are possible safeguards that could be put in place to mitigate some of the long-term risks. However, the question remains whether the potential benefits justify allowing first-in-human clinical trials,” he said.
The public consultation will take place from Friday to Jun 15 this year.