Charlie was eleven months old when he died on 28 July 2017. In that short time, he managed to touch the hearts of millions who followed his story in the media. Charlie died from infantile onset encephalomyopathic mitochondrial DNA depletion syndrome (MDDS) an extremely rare disease with only fifteen recorded cases and none with this variant. It was the result of two mutated RRM2B genes inherited from his parents. Because of the mutations the protein RRM2B necessary for generating nucleosides was absent, hence the DNA in mitochondria could not be formed. Without these powerhouses, the cells responsible for energy production and respiration failed leaving him unable to move or breathe without a ventilator. Such abnormal genes are not unusual; it is estimated that there may be as many as 400 unique mutations in an average human genome. They are autosomal recessive; and therefore of no consequence because they do not manifest unless a copy is acquired. This occurs mainly in consanguineous communities; like the enzyme deficiency syndromes in the Mormons of Short Creek, Utah, USA, and some polygamous West African communities. In this case it was a rare accident.
Treatment is currently only experimental with little evidence of efficacy, and never with anyone who had this variant of the disease. The desperate parents sought help from Dr Michio Hirano from Columbia University who offered experimental treatment in rather questionable circumstances, at a cost of $1.7m. But before this could be attempted, Charlie had setbacks. By mid-December, he began having persistent seizures as his brain function deteriorated. He became deaf, and lacked the ability to breathe, move or open his eyes independently. His heart and kidneys were also started to fail, and it was unclear as to whether or not he was capable of experiencing pain. The Great Ormond Street (UK) doctors felt that further treatment of any nature would be futile. A heart wrenching court battle followed, reaching the SC, and the European Court of Human Rights. Meanwhile Dr Hirano withdrew his offer. The courts all agreed that further treatment was futile and the life support should be switched off. The parents had to give up the fight and accept the inevitable even in the face of offers of help from the Pope and Donald Trump both of which invited adverse comments. The entire episode stirred up a hornet’s nest of legal, ethical, moral and therapeutic debates.
The first issue is whether governments should play a regulatory role in protecting patients from harm by ensuring that unproven therapies must meet a threshold of scientific validity before they are offered, regardless of the ability of the patient to pay. Or should patients be able to purchase treatments of dubious efficacy merely because they can afford it, sometimes exposing the patient, in this case an infant, to harm? Trying to do the best for your child, even in desperate situations, is a powerful driving force. However experts generally feel that therapy should be determined by what is beneficial to the child rather than the ability to pay. American courts are usually reluctant to overrule the wishes of parents, but some states do have a “futile care law”. Canadians have tribunals which generally rule in favour of clinicians. UK courts can act in the best interests of a child and overrule the wishes of families by the legal principle of “parens partriae”; but disagreements between patients and doctors over terminal care of children are rare and eventually settled by consensus in most cases. In India it is generally a free for all; if you can afford it, any mumbo-jumbo is available and accessible. On the contrary prolonged care in ICU’s is generally viewed with suspicion around financial considerations.
The second issue is: who has the final authority to direct that further treatment is futile and the life support systems should be turned off? In India this issue was addressed in the SC judgment in “Aruna Shanbaug vs. Union of India”. The “vegetative state” was described and the distinction between active and passive euthanasia defined. A procedure was laid down for passive euthanasia, because “unscrupulous doctors may fabricate material to show that it is a terminal case with no chance of recovery”. But the procedure was so complex that no state saw fit to adopt it. As a result, we are still in a position where the medical decision is conveyed to the relatives and consent taken for switching off life support. Any ensuing legal tangles are left to the convoluted vagaries of the Indian judicial system.
The third issue relates to the ability to detect the presence of mutated genes which would make life outside the womb impossible. Genetic profiling is now commercially available in India. If an abnormal gene was identified in a fetus, such that life outside the womb would be impossible, would that justify an MTP? Court rulings are already on record permitting MTP because one fetus had severe cardiac abnormalities and another an absent skull, both of which were uncorrectable and incompatible with life outside the womb. Would the same logic apply for a “genetic diagnosis”?
The fourth issue is genetic editing. A new dawn has broken in the ability to correct genetic mutations with Shoukhrat Mitalipov introducing a new technique, the CRISPR-Cas9, to remove the offending gene with a “genetic scissors” without replacing it as was done before. With this technique, genes causing cardiomyopathy and favism, a type of anemia, were successfully corrected. This appears to be the future of human therapy, but it needs close regulation, because it won’t be long before parents start demanding designer babies. After all the Garbh Vigyan Sanskar (Uterus Science Culture) has already institutionalized the concept with their “intimacy protocol” to produce offspring “taller, fairer and smarter”.
Charlie Gard left us with a lot to think about. May his soul rest in the peace he never found in this world.
(The writer is a founder member of the Voluntary Health Association of Goa).
