For the last several weeks, much of the world has been following the tug-of-war between the parents of Charlie Gard and Great Ormond Street Hospital in London.
The hospital initially supported Charlie being treated, in their facility, with an experimental drug that might have slowed the progress of his disease, reduced the severity of his symptoms although it would not be able to reverse any of the existing damage or provide a cure.
However, after Charlie suffered a series of seizures the hospital said he had incurred significant damage to the way in which his brain functioned and that attempting to treat his condition with the experimental drug was no longer in Charlie's best interest. In their medical opinion, it would only prolong his suffering.
At this point, Charlie's parents Chris Gard and Connie Yates decided to initiate court action in an attempt to have Charlie taken to the United States for the experimental treatment.
Around the world, the case has raised questions about the right to experimental therapy, parental rights over their children's well being, the role of the state and the courts in the lives of individuals, how much credence should be given to medical opinion and the right to life.
Some parts of this article have been greatly simplified in order to convey complex scientific and medical concepts.
So, what was the genetic condition Charlie was suffering from? What was the experimental treatment he had been offered? Would the treatment have saved his life? What were the social and cultural impacts of his case?
15 The First Eight Weeks
Charlie Gard was born to parents Chris Gard and Connie Yates on August 4th, 2016 in Bedfont, London. The first child of Gard, a mailman and Yates, a carer was apparently healthy at birth with a regular birth weight and length.
As his first eight weeks past, Charlie’s parents began to notice that their son was not growing and gaining as much weight as the average child. They then noticed that he seemed not to be progressing as other babies of the same age. Charlie did not appear to be able to hold his head up, and they took him to their local family doctor.
Shortly afterward Charlie started to have difficulty breathing, and his parents took him to Great Ormond Street Hospital where he was admitted and placed on a ventilator to breathe for him.
14 A Devastating Diagnosis
As the end of October approached, the doctors started to suspect Charlie had a genetic condition called ‘Mitochondrial DNA Depletion Syndrome’ (MDDS). This is not one but a group of diseases caused by mutated genes. By the middle of November, doctors had confirmed Charlie had the condition, with his particular version being associated with a mutation in a gene for the RRM2B protein.
To be born with the syndrome Charlie had inherited one copy of the mutated gene from his mother and one copy from his father. Charlie's parents had no way of knowing before he was born that they were carrying a faulty gene that would cause such a devastating condition and there was no way of knowing their child was suffering from the condition until after his birth and his MDDS became apparent.
13 What’s MDDS?
‘Mitochondrial DNA depletion syndrome’ actually refers to a group of conditions that cause the body’s tissues to be affected by a drop in the level of mitochondrial DNA in the body’s cells.
In your body, your mitochondrial DNA is responsible for converting the energy from your food into a form that can supply energy to of your cells.
There are a number of things that can go wrong with this. For instance, in some conditions the building blocks to make mitochondrial DNA are not produced in your body so you cannot make more when the mitochondrial DNA you are born with gets used up. Or there is another condition where the mitochondrial DNA in your cells naturally breaks down, and there is a process in your body for recycling the remaining broken bits and pieces into new mitochondrial DNA. In some forms of MDDS, the gene responsible for running the recycling is damaged, and the levels of Mitochondrial DNA in the cells drops.
12 What, Specifically Did Charlie Have?
The particular type of MDDS that Charlie suffered from has only ever been diagnosed in 16 people across the world, including Charlie who had inherited a copy of a faulty gene from each of his parents.
In this case, the gene that controls a substance called RRM2B had mutated and interfered with the production of RRM2B in the body. This, in turn, prevents the cells in the muscles, the brain and the liver having insufficient energy to do their job and the affected body parts start to degenerate, eventually causing irreparable damage.
Typically babies with this condition show a failure to thrive followed by a lack of muscle tone, muscle weakness, motor skill delays, and progressing to kidney disease, a failure of the brain to develop resulting in a smaller head, lactic acidosis, and hearing loss. The condition progresses rapidly leading to a point at which the patient is what doctors politely call “incompatible with life.”
11 The View Of The Doctors
The medical team taking care of Charlie in London's Great Ormond Street Hospital For Sick Children had initially approved the plan to treat Charlie with the experimental drug as it was the only treatment option available.
While doctors were obtaining ethical approval to give Charlie the drug, the little boy had seizures that resulted in irreparable damage to his brain. This meant that, in the doctor's opinion, there was no longer any benefit in giving Charlie the drug. This decision was made because the drug claims to slow down the progression of the disease and to possibly allow the patient to regain some muscle control. The new drug would not be able to reverse any brain damage that had occurred as a result of the seizures or reverse any other organ damage.
A the time of the court case Charlie was reported to have severe brain damage and epilepsy as well as being unable to move, feed or breathe by himself. He was also diagnosed with muscle weakness in his eye meaning his sight would never develop.
10 How The Therapy Works
The help that Charlie's parents were fighting for was an experimental medicine from the US called nucleoside bypass therapy.
The treatment is taken as an oral medication and is designed to provide the body with the building blocks it is unable to produce itself in order to produce mitochondrial DNA. The theory is that by providing the building blocks his body was unable to produce itself, the therapy would help Charlie's body start to make mitochondrial DNA again, and his cells would receive the energy they needed to function.
However, while the medication would be guaranteed to give his body what it needed there was no guarantee that Charlie's body would be able to take absorb it from his digestive system, carry it to where it was needed and use it to begin producing mitochondrial DNA again.
9 No Clinical Trials In The US
The treatment is being developed by Dr. Michio Hirano, a neurologist at Columbia University. However, in the US the drug has not received FDA approval, has not been part of any clinical trial and has not even be tested on mice for Mitochondrial DNA Depletion Syndrome.
Internationally only 18 patients have received the experimental therapy, the majority of which are in Spain and Italy. None of the patients have had the same kind of MDDS as Charlie nor have they been as severely affected.
One person was treated in the US under the special waiver program in which a hospital applies for permission to use a drug which is not FDA approved but which could help a patient with no other options left. If Charlie Gard had been sent to the US Dr. Hirano and Columbia University would have had to apply to the FDA under this program.
8 The US Patient
The patient that was treated under the FDA special waiver program is Arturo Estopinan. Arturo was one when he was diagnosed with TK2-related mitochondrial DNA depletion syndrome, a genetic condition where proteins that help decode DNA break down. This is related but different to the condition from which Charlie Gard suffered.
Arturito spent a year in hospital before being allowed home to a room that is part bedroom part hospital room. The Estopiñans have been taught how to refill the oxygen tanks and to rewire the circuits to his ventilator and how to provide emergency care if the machines keeping Arturo alive fail.
Signs of progress are small. Arturo occasionally makes noises and slightly wiggles his feet, and when his arm is gently lifted up at the elbow, his index finger and thumb faintly move.
His parents buy regular clothes rather than keep him in hospital gowns, but they have to cut the clothes up the back in order to accommodate the medical equipment.
It’s difficult for Arturo's mom Olga her to look at photos of Arturito before he got sick and she refuses to watch video footage of him from his first year of life.
7 The Position In April
During the court case in April, the American doctor gave evidence via phone link from the US and said he was ‘less enthusiastic’ about Charlie flying to the US because he was already ‘in the terminal stages of his illness.’
The doctor said there is ‘a severe dysfunction of Charlie’s brain’ and conceded that treating him would be ‘clearly unchartered territory because no one has done this.' He added: ‘He seems to be very very severely affected neurologically, that makes me a bit less enthusiastic about having him come to the US.’
Sophia Roper, a lawyer for Charlie's parents, asked if their son could be ‘left worse off than he is at the moment’ the doctor said the little boy could ‘continue to deteriorate and he will lose all brain function.'
The doctor also agreed he was ‘not suggesting that it can provide a cure for Charlie’ and that Great Ormond Street Hospital’s application to turn off his life support was a ‘reasonable position.'
6 A New Hope?
At the beginning of June Charlie's parents lost their fight in the supreme court to have their son taken to the US for treatment. By June 20th, the European court of human rights had refused to intervene, and all legal avenues were exhausted.
Great Ormond Street Hospital said there was no rush to turn off the life support and on June 30th, Charlie's parents asked for privacy “while we prepare to say the final goodbye.”
At the beginning of July, Dr. Hirano contacted Great Ormond Street Hospital and Charlie's parents to say he had new evidence to show the therapy could be more beneficial for Charlie than had been previously thought.
In response to this Charlie's parents returned to the high court and asked the judge hearing their case to reconsider and Mr. Justice Francis agreed to review any new evidence.
5 US Doctor Hadn’t Seen Records
Charlie's parents had invited Dr. Hirano to examine their son and provide his expert opinion in January. However, the doctor did not attend in person.
In the July court hearing, Dr. Hirano said that not only had he not seen Charlie in the hospital but he had not viewed Charlie's brain imaging, nor had he read Charlie’s up to date medical records or read the second opinions from other doctors.
Great Ormond Street Hospital granted Dr. Hirano an honorary contract that allowed him all of the privileges of any other doctor at the hospital and made all of Charlie's records available to him. New scans were taken to allow all of the physicians to make an informed decision with the most up to date information.
By the time Dr. Hirano did examine Charlie in person, it was shown that Charlie had suffered severe wasting of his muscle and that the treatment could have no effect on reversing this damage.
4 A False Hope?
After Dr. Hirano and an Italian Dr. had spent five hours with Charlie the Great Ormond Street Hospital released a statement that said:
"When the hospital was informed that the Professor had new laboratory findings causing him to believe NBT would be more beneficial to Charlie than he had previously opined, GOSH’s hope for Charlie and his parents was that that optimism would be confirmed. It was, therefore, with increasing surprise and disappointment that the hospital listened to the Professor’s (Dr. Hirano) fresh evidence to the Court.
“It confirms that while NBT may well assist others in the future, it cannot and could not have assisted Charlie."
The statement went on to say:
"Further, GOSH was concerned to hear the Professor state, for the first time, while in the witness box, that he retains a financial interest in some of the NBT compounds he proposed prescribing for Charlie." Devastatingly, the information obtained since 13 July gives no cause for optimism.
3 Different Legalities
The Charlie Card case would not have happen in the same way in America as it did in the United Kingdom because of the legal differences between the two countries.
In the US there are parental rights, and the views of a child's parents are paramount when making medical decisions. The doctors rarely overrule any choices made by a little one's mom and dad.
In the UK there are parental responsibilities, and the needs of the child are held to be paramount in any decision making. When a child is too young to make their own decisions, a legal representative is appointed. This person has no obligation to the medical profession and no duty to the parents, their sole purpose is to fight for what is best for their child.
2 Ethical Questions
Parental rights and the rights of a patient's next-of-kin raise a number of issues for physicians in the States. The families of patients who are at the end of their life are often, understandably, reluctant to end treatment or to turn off life support.
Many doctors have been asked to take radical measures to keep their patients alive, no matter what the impact on the patient themselves. They have also been asked to keep patients on life support long after all brain activity has ceased or the chance of recovery has passed.
When a hospital and the patient's guardians are in disagreement over treatment options or end of life decisions in the US, it is not unusual for the patient to be moved to another healthcare facility that will comply with their wishes.
1 The Debate Continues
While Charlie Gard's parents ended their fight to have their son treated in the US, there are many ongoing cases in both the UK and the United States where the medical community have one opinion of what is best for a patient and the patient's family have another.
Sometimes the doctors are wrong, and a patient makes a miraculous recovery that was deemed impossible. More often, patients, have life support maintained or are repeatedly aggressively resuscitated because their family has requested that all possible effort is put into keeping someone alive.
The family are either grieving a death or maintaining false hope that they will have their loved one back. Doctors do not want to continue life support for someone once it is past helpful, but they do not want their patients to die. These are the cases in which nobody wins.
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Tyynismaa H, Ylikallio E, Patel M, Molnar MJ, Haller RG, Suomalainen A. A heterozygous truncating mutation in RRM2B causes autosomal-dominant progressive external ophthalmoplegia with multiple mtDNA deletions. Am J Hum Genet. 2009;85:290–295. doi: 10.1016/j.ajhg.2009.07.009
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