For American conservatives, Britain’s NHS is an antiquated Orwellian dystopia. For Brits, even those who don’t love the NHS, American conservatives are better suited to spaghetti westerns, such as Fistful of Dollars, than reality.
The twain is unlikely to meet after the recent press surrounding Charlie Gard the infant, now deceased, with a rare, fatal mitochondrial disorder in which mitochondrial DNA is depleted – mitochondrial depletion disorder (MDD). In this condition, the cells lose their power supply and tissues, notably in the brain, die progressively and rapidly.
The courts forbade Charlie’s parents from taking him for a last dash of hope to the United States. This confirmed for many conservatives the perils of a government-run healthcare system, where the state decides who lives and who dies through Death Panels.
Ted and Mike, whose healthcare reform might affect many curable little Charlies, were moved by the plight of an incurable Charlie. No European will understand the science behind their sentiment – if you care so much about a sick incurable baby, why don’t you care about sick, curable babies, they’d ask.
Brits will never get the importance conservatives place on individual choice, even if that choice is forlorn, and of the lure of medical heroism. Conservatives seldom acknowledge that modern medicine reaches its limitations too quickly for Death Panels to be effective. Charlie was given a grim prognosis by doctors at the Great Ormond Street Hospital (GOSH), arguably the finest hospital for sick children in the world.
GOSH might not have the endowments of its American counterparts. It is an orthodox British hospital with creaking staircases, the sort where I trained, where doctors have incredible clinical acumen, paranormal common sense, and dabble freely in paternalism. Doctors know best and are not ashamed to say so. When doctors at GOSH say death is imminent, Death Panelists are rendered unemployed, unless there’s a miracle to slay. For Charlie, that miracle was a New York neurologist offering an untested therapy.
The reaction to Charlie’s plight is as instructive as the reaction to the reaction to his plight. It’s as if everyone took the Rorschach test simultaneously.
Charlie’s plight was felt by the Pope. The Pontiff is a busy chap and can’t possibly Tweet in support of every dying child in GOSH. But once the media portrayed his suffering, everyone jumped on the bandwagon. The Pope was joined by Ted Cruz, Donald Trump, Theresa May, Nigel Farage and even the notoriously unsentimental Jeremy Corbyn. This is the power of the identifiable victim.
Some have wondered whether our preoccupation with stories such as Charlie’s diverts our moral and financial resources from tackling deaths from malaria in Africa – i.e. we don’t care about deaths from malaria because we care too much about one dying infant. In this classic utilitarian fallacy, the utilitarian treats moral sentiments as a zero-sum game with opportunity costs. The truth, as Adam Smith pointed out in Theory of Moral Sentiments, is that we’ll always be more perturbed by events proximate to us, the identifiable victim, than random people who don’t appear on our Twitter timeline. If Charlie hadn’t surfaced in our news channels, we still wouldn’t be fretting about deaths from malaria in far off countries we’ve never heard about.
Charlie’s case showed the limitations of not just modern medicine but modern medical ethics.
When all hopes seemed lost, Charlie’s parents did what many do today – they consulted Dr. Google, who didn’t disappoint. Their search revealed a New York neurologist – Dr. Michio Hirano, a researcher and an expert in mitochondrial disorders.
When hope resurfaced so did the controversy. The first point of controversy was that the nucleoside therapy Dr. Hirano was offering was not scientific – i.e. there was no proven benefit of the nucleoside in the specific variant (RRM2B) of Charlie’s MDD – it hadn’t even been tested on animals with that variant. GOSH, the High Court and the terribly unoriginal European Court, used the absence of proven efficacy in their justification for stopping the parents from taking the child to the US.
“Not scientific”, a compelling statement as no one can argue with science, needs parsing. It is possible for a treatment for a rare disease to have promising results in a small trial in the US, but still not be available in the NHS either because the National Institute of Clinical Excellence (NICE) hasn’t gotten around to approving it or is waiting for more evidence. This wasn’t the case with Charlie’s disorder, but my point is what may be unscientific today may truly be unscientific or may simply be waiting for NICE to schedule a conference call.
Charlie would have been the first patient with the RRM2B variant to have received the nucleoside therapy. Though we don’t know for certain, it is highly unlikely Charlie would have responded favorably. Had he responded favorably, the treatment’s efficacy would be certain. This is because Charlie’s condition had a 100 % fatality and anything that’d have saved him, gotten him off the ventilator and breathing spontaneously, and restored his motor function, would either be a parachute or a prophet – you don’t need a double blind, placebo-controlled, randomized controlled trial to test the efficacy of a drug for a condition which is imminently and uniformly fatal.
The neurologist was accused of having financially conflict of interest in nucleoside therapy, which he has strongly denied.
This familiar moral dilemma, which brings science closer to morality than necessary, begs legitimate questions. Was the doctor genuinely motivated by a desire to help or by making more money? Was there truly therapeutic equipoise or was he selling snake oil?
Science being morally neutral means that the neurologist’s motivation for helping was moot. The therapy either worked or didn’t. And if it worked no one would care if the doctor is Satan. If it didn’t work it scant mattered if he were the Pontiff. His financial conflict of interest is relevant only because it indicates whether equipoise – i.e. that the therapy may work – is justified.
To emphasize, we must believe that science, i.e. proven treatment benefits, is morally neutral – because it would be silly not to – I mean it’d be like saying a treatment would work better if the prescribing doctor were more pious.
But, seemingly, equipoise is not morally neutral. What we’re saying is that the uncertainty, and I repeat the uncertainty, that a treatment may work depends, to some extent, on the motivations of who is calling the experiment. This is understandable because medicine is replete with stories of sellers of snake oil. But there’s a large coastline of plausibility far removed from snake oil.
Dr. Hirano wasn’t selling snake oil. He was selling a plausible but untested treatment to desperate parents. The nucleoside therapy had modest efficacy in a variant of Charlie’s disorder (TK 2). But had never been tested in the RR2MB mutation, which Charlie had. It was unscientific because it was unproven – it wasn’t implausible – it certainly wasn’t snake oil.
Ironically, precision medicine exposed the unscientific nature of the nucleoside therapy. Imagine if you couldn’t sequence. You wouldn’t know that MDD had variants – that is you wouldn’t know whether Charlie’s MDD was the TK2 or the RR2MB variant, it’d all be the same. Would the nucleoside therapy, which had worked in a handful of patients with the TK2 variant, still have been unscientific? This is not a dig against precision medicine. I’m merely asking for less dogmatism in what we call unscientific, given that the line is so thin between groups in which therapies work and don’t work.
This takes me to the desperation of Charlie’s parents. I can’t even begin to imagine what they were going through. I recall how I reacted at the very slight possibility that my older son, when he was three weeks old, had pyloric stenosis. My frontal lobe stopped working. Were I Charlie’s parents, I’d have fought tooth and nail and eked every possibility. I’d have done exactly what they did.
Parents of children who have terminal illnesses have nothing to lose, so they pursue any hope, no matter how hopeless the hope is. Some ethicists find this sentiment repugnant. You can see why the ethicist’s ire is drawn. Picture this – desperate parents willing to do anything, offered false hope by a doctor who knows that their condition is hopeless, who knows the treatment is unproven, and who is merely taking advantage of their predicament, like a parasite. Won’t you be disgusted by that doctor?
Let’s reframe this. A doctor offers hope to desperate parents who have nothing to lose except hope itself. The doctor believes that denying hope, no matter how hopeless, will be crueler than giving hope. Incidentally, Lord Krishna, one of the many Gods of Hindus, said that a lie which makes someone feel better is better than a thousand truths which make a person feel worse.
Are you still disgusted with the doctor prescribing hope? I’d say “repugnance” is a rather strong sentiment in this ethical gray zone, where the answer depends on how the situation is framed. To believe medical ethics is as absolute as Newton’s Third Law of Motion betrays an alarming level of judgment.
Charlie would have been the first to receive the nucleoside therapy for his condition. In any trial of medical treatment, there is always an index patient – the first to receive the unproven therapy. This is an inviolable fact, whether the unproven therapy later proves itself or not.
Would we be offended if Charlie was the first to receive the unproven treatment as part of a research trial with a hypothesis where the researcher purposefully set out to collect data and specified the outcomes in advance?
It was unethical to experiment unproven therapy with Charlie. Paradoxically, it was also unethical to give Charlie unproven treatment because it wasn’t an experiment.
What then in modern era is the difference between a neurologist responding to desperate parents by giving unproven therapy and a neurologist responding to desperate parents by giving unproven therapy as part of a trial? It’s easy seeing that both scenarios are experimental. But there is a difference. The latter comes with regulatory oversight, the former doesn’t. So, a major gripe here is the absence of regulatory oversight.
This wouldn’t have been the first-time unproven therapy has been offered to sick children with fatal conditions short circuiting a trial. Take the case of surgery for complex congenital heart diseases such as Hypoplastic Left Heart Syndrome. The first time a surgeon operated on a neonate with this condition, the treatment was unproven and, therefore, unscientific. The treatment was offered to desperate parents who believed they had nothing to lose. Indeed, the operative morbidity and mortality for early cardiac surgery for congenital heart disease was so high that whatever short life span these babies had was curtailed by the surgery – i.e. surgery made matters worse. Then the heart surgeons learnt from their errors, improved their technique and patients lived longer. Today, patients with complex congenital heart disease are old enough to worry about cancer and dementia.
Again, the ethics of offering an unproven treatment to a sick child of desperate parents is trickier than first appears. While it may make us balk, the first few recipients of unproven therapy can be made worse, even if the therapy later does net good. I’m not terribly fond of utilitarian reasoning – greatest good to the greatest number – but utilitarianism makes its way through multiple avenues. One argument, which I’m partial to, is that if you relax the access to therapies which haven’t been adequately scientifically vetted for rare diseases with no cures, drug developers will have little incentive to produce genuine cures. This is a compelling and highly plausible conjecture, but it is utilitarian at its core – i.e. we believe that easy access for a few could lead to net harms for many.
Some have defended the action of GOSH by saying it is not about costs, only effectiveness. This is understandable – no one wants to muddy the issue by talking about costs – but disingenuous. Of course, costs are important when the taxpayer is footing the bill. Charlie was ventilated. He’d have to be shifted by air ambulance and accompanied by trained personnel. Medical resources aren’t free even in the NHS. And given that the effectiveness of the nucleoside therapy is nearly zero, the cost-effectiveness would be nearly infinite.
Charlie’s parents had raised funds to help with the costs. This evokes a familiar sentiment in the NHS – should they be allowed to pursue treatment simply because they can afford it? The NHS prides itself, rightly so, on equity – no one is denied proven treatment because of inability to pay. But it’s hard seeing how equity is disrupted if someone decides to pay for futile treatment. Furthermore, Britain has a parallel private system in which proven treatment is accelerated for those who can pay. The Brits, when they want, seem perfectly capable of tolerating inequity.
The crux of the matter was the tension between the welfare of the child and the wishes of the parents. When I was a junior doctor working in an emergency department in London, we were counselled not to bow to the demands of parents and prescribe antibiotics for febrile children. Doctors, even junior doctors, knew best.
The trickier situation is when parents refuse treatment for their sick child. Doctors have the law on their side here and you can understand why. If parents of a child with meningococcal septicemia are conscientious objectors of synthetic therapy and decide that antibiotics for meningitis aren’t indicated, their wishes can’t supersede medical necessity. That is if parents clash with doctors, the doctors will prevail, and the child will receive life-saving antibiotics against the wishes of the parents, and rightly so. Let me state this in no uncertain terms – the courts agree that doctors know best.
Neither medical paternalism, nor the fight against it, is absolute. Doctors do know best, but “best” is a spectrum. For example, the courts can’t force a child to be vaccinated against the wishes of the parents. Few would dispute that vaccinations are beneficial to both the individual and society. But the courts distinguish between a proximate harm and a probabilistic harm to the child.
Would subjecting Charlie to unproven therapy worsen his welfare? Arguably, yes – there’s a fate worse than death, and being on a ventilator prolonging death senselessly is a form of suffering, no less because it can’t be articulated. Does this come under the antibiotics – meningitis domain (proximate harm) or the vaccination domain (probabilistic harm)? I’d be inclined to put it towards the former, unless I was Charlie’s parents. But you can see that this, too, is in the ethical gray zone.
There’s no doubt that the doctors in GOSH made a good clinical call. But every now and then the medical profession encounters an outlier and responding to an outlier needs more than clinical acumen.
The matter reached the European Court – an institution which excels itself at irrelevance by saying nothing new. It’s hard not concluding that a drama was made of a crisis in a tricky realm where each actor wanted to stamp their absolutism. Would it really have been the world’s greatest travesty if Charlie had been taken to the US to receive an unproven therapy? Could GOSH have handled the matter more prudently? Was a legal injunction really necessary? Could the NHS have avoided been morally scolded by Ted Cruz?
Of note, when Dr. Hirano examined Charlie at GOSH he concluded that the brain damage could not be reversed. Perhaps if the doctors at GOSH had incorporated Dr. Hirano as part of their multidisciplinary team at the outset, thus respecting the parent’s preferences, the legal drama could have been avoided. NHS hospitals have something to learn from their American counterparts.
For conservatives, the Charlie Gard story affirms that the NHS is a tyrannical apparatus which conspires to rob people of their fundamental human rights and that Brits submit meekly to medical paternalism. In this tragic story, no one has been more naively absolutist than the conservatives. Calling the NHS “tyrannical” when it saves many poor kids without bankrupting their parents is absurd. This noble institution could, however, do with better PR, because it has come across as inflexible and dogmatic instead of compassionate and scientific. For both the National Health Service and the Great Ormond Street Hospital, this is a huge travesty.
Saurabh Jha is a contributing editor to THCB.
It seems that the Great Ormond Street Hospital had reached out to Dr. Hirano in January this year, asking he visit the baby and clinically assess him. While this may not have changed the outcome, nor the tricky ethical issues surrounding this case, it does mean that GOSH was more accommodating than I had alluded to.
Nice, though I wish you had known and placed into the heart of your article that GOSH had indeed reached out to Hirano in January. I suspect hat changes the tenor of your piece a bit. I think this was a tough decision and don’t those involved. The part I don’t see you acknowledging (Post-call so maybe I just missed it) is that the courts needed to weigh the welfare of the child against the desires of the parents, i.e. if the cost of bringing hope to the child was pain and suffering on the part of the child with no hope for improvement, then someone had to stand up for the child. OTOH, if the child was beyond suffering, then maybe the cost of hope was not so high. If there was hope for improvement, then that is a different balance. Given that the neurologist finally did see the child and concluded that the damage was not reversible, it was still a tough decision but seems pretty reasonable.
Query- You really think it would be better if hospitals put a much higher priority on PR?
Dr. Jha, easily a most thoughtful analysis of the complexities of a young child with a progressive terminal genetic disease. It is very difficult for any parent to reconcile their hopes for a normal child to raise and the reality of a disability. Even with children born with Trisomy 23, Down’s Syndrome, it may take 3 years to finally accept the privilege of living with such a wonderful person. They also realize that their entire family views life in a more positive realm. It is not always that easy no matter what the infant’s disability represents.
I would only add that dependence on a ventilator offers very little dignity. It seems that dignity is ultimately the ethical standard that is most important at the end, rather than waiting for a terminal event such as pneumonia or a healthcare misadventure. Finally, no mention was made of an Institutional Review Board involvement by Dr. Hirano with any care offered in the United States.
Try to recall the bugs that live intracellularly: Bartonella, tularensis, listeria, salmonella typhi, brucella, legionella, mycobacteria, nocardia, Rhodococci, yersinia, neisseria, viruses, rickettsia, and……..yep, some type of bug that became our mitochondria millions of years ago. So we have a great clue to treat mitochondrial diseases: put the 34 genes from some normal mitochondtria on some intracellular micro-organism, or on some rickettsia or virus, and infect the child.
Hope for best.
People who have hopeless diseases should be able to do whatever they want as long as the treating entity does not gypp them.
37 genes, not 34