Tuesday, July 18, 2017

Charlie Gard 5

Since mitochondria are the location of some important cellular functions, it will come as no surprise that mutations in mitochondrial DNA can be just as problematic as mutations in our gDNA — and depletion of a large amount of mtDNA can have serious consequences. Though there are varying causes of MDDS, in Charlie’s case, it was caused by a mutation on a gene called RRM2B. What does RRM2B do? Like most genes, it’s a sequence of four bases, known as A, T, C, and G, encoding the information a cell needs to create a protein, in this case an enzyme (a molecule that can make changes to other molecules) called RRM2B —  scientists tell the difference between a gene and a protein by using typography; while RRM2B is the name of the gene, RRM2B is the name of the protein created by the RRM2B gene. RRM2B is an enzyme crucial the production of mtDNA, thus the absence of a healthy RRM2B leads to a depletion in mitochondrial DNA – and in turn to MDDS. Though mitochondria depend on their mtDNA to function, but this mtDNA itself is maintained by enzymes encoded for in gDNA; so a mutation in the genetic DNA contained in the cell’s nucleus leads to the depletion of mitochondrial DNA, which means mitochondria shut down, meaning that organs and tissues don’t get the energy that they need to function. The result: multi-organ failure — and the lethal disorder from which Charlie suffers…

MDDS when caused by an RRM2B mutation makes its presence known at a very young age, and often affects the nervous system. There are different forms of MDDS though, which manifest in different ways, and with widely varying symptoms. As of 2013, there were only 15 known cases of RRM2B-caused MDDS – which goes some way to explain the paucity of research into this particular syndrome. Nonetheless, several early-stage studies have looked into possible pharmacological treatments, though only in mice and cells cultured in a petri dish. The approach has been dubbed nucleoside treatment. This is not a cure or magic bullet, but a pharmacological treatment to reduce symptoms, improve quality of life and life expectancy. Essentially, it is thought that some forms of MDDS, including Charlie’s, are caused by a lack of the building block needed to produce DNA, deoxynucleotide triphosphate, or dNTP — so the thinking that supplying cells with dNTP will allow them to replace the depleted mtDNA, and — hopefully — to function properly, avoiding multi-organ shutdown.

Studies of this therapy are thin on the ground, but a paper published in EMBO Molecular Medicine in 2014 presents the most advanced piece of research yet: Dr Caterina Garone and colleagues show that treating mice afflicted with MDDS caused by a mutation on the TK2 gene saw their lifespan increased by twenty days, from 13 to 34, when infused with molecules that can be converted to dNTP — with scope for further improvements at higher doses. Unfortunately, another paper seems to indicate that there would be no improvement in RRM2B-MDDS — the variant that Charlie Gard has. On July 13, an anonymous American professor called in by the White House claimed that nucleoside treatment alleviated symptoms for a less severe form of MDDMS in five out of nine paediatric patients, but his claims are not published data.

There is a seemingly simple calculus behind the choice to send Charlie Gard to America for nucleoside therapy — will the therapy alleviate the boy’s suffering? But as with every simple-sounding ethical problem, there are a multitude of complex questions roiling away under the surface. The evidence presented by the White House’s physician, albeit unpublished, will have to be taken into account by the court. At present, an American doctor, Dr Hirano is presenting his own examination of Charlie to the court, which is not due to make a decision until June 25. The sad and circuitous case of Charlie Gard continues.


Bulst S, Holinski-Feder E, Payne B, Abicht A, Krause S, Lochm├╝ller H, Chinnery PF, Walter MC, Horvath R. In vitro supplementation with deoxynucleoside monophosphates rescues mitochondrial DNA depletion. Mol Genet Metab. 2012 Sep;107(1-2):95-103. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038513/

Mitochondrial DNA depletion syndromes are a genetically heterogeneous group of often severe diseases, characterized by reduced cellular mitochondrial DNA content. Investigation of potential therapeutic strategies for mitochondrial DNA depletion syndromes will be dependent on good model systems. We have previously suggested that myotubes may be the optimal model system for such studies. Here we firstly validate this technique in a diverse range of cells of patients with mitochondrial DNA depletion syndromes, showing contrasting effects in cell lines from genetically and phenotypically differing patients. Secondly, we developed a putative therapeutic approach using variable combinations of deoxynucleoside monophosphates in different types of mitochondrial DNA depletion syndromes, showing near normalization of mitochondrial DNA content in many cases. Furthermore, we used nucleoside reverse transcriptase inhibitors to precisely titrate mtDNA depletion in vitro. In this manner we can unmask a physiological defect in mitochondrial depletion syndrome cell lines which is also ameliorated by deoxynucleoside monophosphate supplementation. Finally, we have extended this model to study fibroblasts after myogenic transdifferentiation by MyoD transfection, which similar to primary myotubes also showed deoxynucleoside monophosphate responsive mitochondrial DNA depletion in vitro, thus providing a more convenient method for deriving future models of mitochondrial DNA depletion. Our results suggest that using different combinations of deoxynucleoside monophosphates depending on the primary gene defect and molecular mechanism may be a possible therapeutic approach for many patients with mitochondrial DNA depletion syndromes and is worthy of further clinical investigation.

Fromm the paper

Myoblasts of a patient, carrying autosomal recessive RRM2B mutations showed different results in vitro studies. RRM2B (p53R2) affects dNDP synthesis, by transforming rNDP to dNDP, which is supported by the fact that mutations in the RRM2B gene lead to decreased cytosolic reduction of rNDP to dNDP. As previously described, the two homodimers R1 and R2 of the ribonucleotide reductase (RNR) are essential for dNDP synthesis during S-phase while the R1–p53R2 complex (p53R2 encoded by RRM2B gene) enables dNDP synthesis on a cell cycle independent manner . Therefore p53R2 supplies dNDPs for mtDNA replication  and possibly enables dNDP synthesis for DNA repair after DNA damage. Unlike DGUOK or POLG deficiency, RRM2B deficient myoblasts had significantly lower mtDNA copy number, and no further decrease was observed in myotubes. Supplementation with dNMPs did not result in any change of mtDNA copy number. We can draw two conclusions from these results. First we suggest that not only myotubes (post-mitotic cells), but also myoblasts and possibly other dividing cells can show mtDNA depletion in RRM2B deficiency. Second, supplementation with dNMPs, as expected, had no beneficial effect in RRM2B deficiency. Based on the function of this protein supplementation with dNDPs could be tried as an alternative strategy in RRM2B deficiency.



    The therapy supplies the building blocks of DNA. Charlie has a mutation in a gene called RRM2B, which codes for the production of an enzyme that helps produce the four “letters” (nucleotides) that constitute DNA in mitochondria.
    A mutated gene produces a dysfunctional enzyme; without a functional enzyme, mitochondria can’t replace DNA that’s damaged or deteriorated. Eventually, mitochondria—and the cells they power—stop working, with devastating effects especially on cells of the muscles and brain. Nucleosides are precursors to nucleotides; they’re turned into the latter in the body, providing the missing components of DNA.


    Hirano told a recent science meeting that 18 patients, most of them in Spain and Italy, are receiving nucleoside bypass therapy. At the June Mitochondrial Medicine symposium, which drew some 330 researchers and physicians to Alexandria, Va., Hirano described the research, two people who attended the meeting told STAT. (Hirano, a neurologist who specializes in neuromuscular diseases, did not reply to requests for comment and Columbia declined to answer any.)
    Nucleoside therapy “seems to be safe and well tolerated,” said Charles Mohan, Jr., CEO of the United Mitochondrial Disease Foundation, a patient advocacy group that funds research and which organized the Alexandria meeting.


    Not exactly. They all have a mutation in the TK2 gene, not RRM2B. Both mutations produce mitochondrial DNA depletion. The most publicized TK2 patient is Arturito Estopinan, who was born with TK2 disease in 2011 and has been treated by Hirano since he was 1. At first Arturito received nucleotides, the actual building blocks of DNA, but after two years he was switched to nucleosides, which are better able to survive the gastrointestinal tract and reach cells and their mitochondria.
    Arturito’s respiratory function and strength have improved noticeably on nucleoside therapy, Art Estopinan, his father, said: He can now move his fingers, hands, and toes, and sit (with support) at a 90 degree angle for 90 minutes compared to a 45 degree angle for 15 minutes previously.


    Under a “compassionate use” exemption from the U.S. Food and Drug Administration, a program that allows patients who are otherwise out of options to receive experimental drugs that have not been approved by the FDA, he could receive the therapy in New York City. (Columbia said on July 6 that it is willing to treat Charlie.) It doesn’t involve any red tape: The FDA typically okays such use in a single phone call with the scientist.
    Hirano is expected to examine Charlie Monday and Tuesday, after which Hirano could make the request to the FDA.


    “A proper clinical trial has not started,” said Dr. Fernando Scaglia, professor of medical and human genetics at Baylor College of Medicine. A biotech investment company called Aceras BioMedical has been asking physicians who treat patients with mitochondrial disease if they would be willing to participate in a clinical trial of nucleoside therapy for TK2 patients like Arturito, perhaps as early as next year. “But no one is talking about RRM2B,” the form of the disease that Charlie (and reportedly only 15 other patients in the world) has, Scaglia added.


  2. An attentive world is watching, aghast, at the troubling tug-of-war over a terminally ill baby boy in a London hospital. On one side are the distraught and devoted parents who want to shoulder the cost of a treatment that reportedly has little chance of success.
    On the other side is a medical and state bureaucracy that is insisting, instead, on turning off the baby's ventilator and allowing him to die.

    The case of Charlie Gard is creating anxiety for spectators everywhere as they observe the locus of control over difficult end-of-life decisions pass from the intimate family and doctor unit to an impersonal and distant state.

    In watching Charlie's case we learn that with government-run or socialized medicine, not only can the state refuse to provide life-extending care, it can deny us the freedom to pay for it ourselves, to leave the country seeking an alternative treatment and even to go home to die.

    Now this is not, as some thoughtful commentators have rightfully observed, an instance of the state demanding euthanasia. Removing the baby's ventilator will cause him to die naturally, and mechanical ventilation, unlike hydration and tube feedings, is typically considered an extraordinary measure that is not ethically obligatory when all hope for a cure is gone. (continued)

  3. (continued) And yet, these same commentators seem to have a touching faith in the ability of distant courts and hospital ethics boards to choose what surely everyone desires for themselves and their loved ones: A course of action that errs on the side of hope and life.

    But it's impossible to share that faith when in Europe (further along in applying a utilitarian view of life than the United States), hospitals in countries like Belgium increasingly per
    form involuntary euthanasia, the unethical practice that errs on the side of death and hopelessness.

    The traditional approach to end-of-life issues in Western medicine, which most American physicians and patients would like to preserve, is that decisions like pursuing another course of chemo, continuing life support or seeking slim-hope treatments should be left to the judgment of the patient or the patient's proxies. This is especially the case when the patient is not in great pain and will not be gravely harmed by further interventions, and it is most relevant when the patient is a child, as children have a remarkable capacity for healing and recuperation.

    Of course, there is the very real and human problem of denial in the face of painful realities. Sometimes, we struggle to "let go." Sometimes, out of fear of death and separation, we grasp at straws, refuse to accept the inevitable, and prolong an already painful process.

    Many of us have seen situations where a terminal diagnosis is rejected by loving family members who demand yet another round of punishing chemotherapy, even if the patient has accepted their fate and is prepared to part in peace. This problem is exacerbated by an increasingly secular culture that has largely lost faith in a loving providence and the hope of meeting beloved ones in heaven.

    Physicians and nurses who accompany patients and their families at the end of life know that they are going through a difficult process that requires gentle explanations, patience and compassion. Every individual and family moves at a different pace along the painful path of accepting death. In the most humane and least traumatic scenario, an intimate relationship between the suffering and their caregivers enables the patient "to go gently into that good night" without unseemly haste and certainly without force.

    But in the case of baby Charlie, we are confronted by the sight of the mighty state using force, choosing the exact moment when the ventilator is removed and the baby will suffocate. And this is despite the fact that the boy's miserable mother and father are not even asking for state funds to keep their child alive. As they said, "We've ... never asked the hospital, courts, or anyone for anything, only permission to go." Such use of force is so disturbing it can create a sense of trauma felt by complete strangers across the world.

    It may very well be that the treatment his parents so desperately desire for him cannot or will not help Charlie Gard. Nevertheless, millions of people across the world are rooting for Charlie, hoping he gets the chance to at least try. This baby boy has become an icon in the battle to keep our end-of-life path grounded in the appreciation of the great value of each human life. So may it be that the tug-of-war ends such that he, and everyone else, is kept far away from the soulless, utilitarian grasp of bureaucracy, and is instead allowed to be supported by the compassionate care of doctors and the love and devotion of family.


  4. The experimental therapy that has been suggested for Charlie would be an oral medicine that aims to deliver the correct type of nucleoside to improve the function of his mitochondrial DNA.

    The medication has been tested on mice and a small number of people with a different mitochondrial condition, some of whom have shown measurable improvement.

    But the drug has never been tested on people with Charlie's specific condition. As a result, the baby's response to the experimental treatment is difficult to predict.

    ABC News' "Nightline" reported on an American family from Baltimore who understands the trying circumstances for Charlie’s parents and recommends the experimental treatment.

    Art and Olga Estopinan’s 6-year-old son Art Jr. was diagnosed with a similar type of mitochondrial depletion syndrome when he was just over a year old. Like Charlie, doctors had told his parents there was little chance of survival.

    Five years ago, Art Jr. became the first child in the U.S. to receive the treatment and Hirano was the doctor who administered it.

    "We were told there was no hope and no cure," Olga Estopinan told "Nightline." "He was terminal and the average age for these children was 3 years old."

    The Estopinans said little Art Jr. went from being on the brink of death to gaining back some motor functions. He can now find and play movies on an iPad and say "Mommy," "Daddy" and a few other words.

    The medicine has not "cured" Art Jr. He requires round-the-clock care, receives three to four treatments per day, eats through a feeding tube, uses a motorized wheelchair and needs help moving his limbs, "Nightline" reported.

    Despite those challenges, Art Jr.'s family said it has changed their son's life and recommend it.

    "With all due respect to [Charlie’s doctors,] I encourage those doctors to educate themselves," Art Estopinan told "Nightline." "See how these experimental medications will create the end signs that little Charlie needs so he can get stronger like my son."


  5. Let me stipulate that I have friends who are physicians, and very good physicians. Part of what makes them good physicians is the fact that they are aware of all they do not know — that “there are more things in heaven and earth than are dreamt of” in their training, their copious studies, and their medicine bags. Medicine is a science, and it’s a science that, as one doctor-friend of mine has said, “pretty much requires that the scientific method be applied to each patient, in every circumstance, because every person is different, and we really don’t know everything.”

    And because that’s true, my friend maintains, medicine is also an art, one that requires a physician to approach every patient with a bit of wondering. In the same way that a writer sits down with a sure sense of what she wants to write yet often ends up surprised by the turn her words take, and by her own conclusion, a doctor who is willing to admit wonder into an assessment is often surprised by all he has not known.

    Medical bureaucracies that forget that healing is also an art — which therefore must make room for wonder, and be willing to question “obvious” conclusions — become the sort of bodies that prefer to err on the side of death, and increasingly I believe it’s because they are so afraid of what life might throw their way. They want to function under a pretense of certainty and an illusion of control; uncertainty has no place in their practice, because it may permit something that is complicated and scary, (and potentially very expensive).

    Death is safer; it is certain, and permits no unruly chance-taking. It is fear of uncertainty, I think, that makes a doctor feel alright about (absurdly) saying to parents “you should abort this fetus, because he won’t even be a human being.” (continued)

  6. (continued)Really, if a doctor is telling you the child in your womb “won’t even be a human being” it’s time to find a better, less fearful, scientist. One who has not lost touch with healing as an art. One you can bring your happy, healthy, beloved four year-old to visit, sometime.

    The parents of a little boy in the UK were told to abort him, because his brain was not developing. Turns out he’s keeping up pretty well, now. A little slower than some, but alive, happy, going to school, loving and being loved.

    And that’s the key thing — the loving and being loved thing, that so many have lost sight of in the Charlie Gard case. Doctors admit they have no idea whether Charlie Gard is feeling pain, but they sure don’t like all of the messy, expensive, and emotionally draining uncertainty about him. Charlie’s life has become an inefficient inconclusion because of love — that untidy, unsterile, unreasonable thing that keeps the scary unknown before them and denies death its simple solution.

    In the Wall Street Journal, William McGurn writes, “The Great OrmonUnsterild Street Hospital even wants the last word on love: ‘In one respect, Charlie is immensely fortunate’ to have such loving parents. Because in this context ‘in one respect’ really means, ‘not in the sense that has to do with decisions about their son’s life.’ In other words, the parents’ love disqualifies them.”

    Medicine is a science, and as science it wants controllable outcomes. But medicine is also an art, which can imagine more, if it really wants to. Both art and science, however, must remain subject to love, and constrained by love’s choice for life over death, if they are not to become mere and monstrous regimens.

    People worry about the “quality” of a life — a subjective thing they want to pretend is objective. Doctors and death-advocates will argue that a human being’s “quality of life” is (or will become) such that it seems “merciful” to deny that life. But all of us will eventually see a diminishment to our “quality of life” at some point; should all of us simply prepare for the day we lose consciousness, hear someone declare, “well, that’s it, she’s done” and be given an “efficient” injection? How many stories do we read of “brain dead” people who come out of it reporting that even when “brain dead” they were hearing, and feeling, and loving, and being loved?

    We read stories about parents who chose to bring their “doomed” children into the world rather than aborting them, who permit themselves to experience so much pain and loss (as if an abortion alternative is a static event that precludes both) but what do we see in those stories? We see a celebration of a life, amid a searing brevity.

    We also see how, in even the briefest life, there is a chance to kiss, and hold, and whisper words of love — a chance to affirm a life loved into being, a personhood real, unique and unforgettable.

    However brief, however unsightly and mysterious, however untidy that life becomes in a day, or five, or in ninety years, it is the life a person has. And a person is entitled to it.

    To love, and be loved — to feel love at its heights and depths, in its euphoria and sorrow — to invite love into the world, in all of its fullness and purity and pain and to make it welcome, this is what sustains light over darkness.

    With each new life we permit entry into the world, new love comes into the world, too. The world needs that love, for the light it brings. And because love never dies.

    It is the art of God, and it merely begs our cooperation.


  7. The British parents of critically ill baby Charlie Gard have been told by a hospital lawyer that the results of their son's latest brain scans make for "sad reading."

    Great Ormond Street Hospital lawyer Katie Gollop broke the bad news to Charlie's parents at a pre-court hearing Friday in London.

    Charlie's father, Chris Gard, yelled "Evil!" at Gollop as his mother, Connie Yates, began to cry. The parents said at the hearing it was the first time they were being told about the latest results in the crucial test of Charlie's brain function.

    The hospital believes that 11-month-old Charlie has suffered irreversible brain damage that treatment cannot repair. His parents disagree. Earlier this week, Charlie underwent brain scans in an attempt to determine whether his brain damage is irreversible.

    The results of the scans were not made public.

    The pre-hearing Friday was the latest step in his parents' long legal battle to give Charlie, who suffers from mitochondrial depletion syndrome and cannot breathe unaided, an experimental treatment. They believe the treatment, which has never been tested on a human with Charlie's exact condition, could restore his muscular and brain functions.

    It's not clear how much longer Charlie can live without the treatment.


  8. Rep. Jaime Herrera Beutler (R-WA) gave a very personal and moving testimony Tuesday in support of her amendment, which ultimately passed, to grant 11-month-old Charlie Gard permanent residency in the United States so that he could come for an experimental treatment for his rare genetic condition. Beutler was once in an extremely similar situation with her own daughter.

    Her daughter Abigail was diagnosed in the womb with the rare genetic condition, Potter’s Syndrome, a fatal diagnosis meaning that the baby had no kidneys. Rejecting the advice of doctors to get an abortion, Beutler received the experimental treatment of saline injections during her pregnancy as a substitute for the amniotic fluid absent due to the unborn baby’s missing kidneys.

    Abigail is the first baby to survive birth without kidneys and her story has helped other babies who survived due to that same treatment. She later received a kidney transplant from her father, Daniel Beutler.

    Charlie Gard’s parents are currently in a court battle to let him access an experimental treatment as the Great Ormond Street Hospital in London where he is being held would like to remove his life support and believe the treatment would only prolong his suffering.

    Beutler called her amendment “an opportunity for us to stand with a family who are right now fighting for their son’s life.”

    “The reason I’m moving this amendment,” she emphasized, “is because I strongly believe having faced circumstances, similar circumstances, that parents have the most at stake when it comes to standing up for their children.”

    A happy, healthy Abigail joined her mother during votes Wednesday who tweeted that voting “got a little more fun with the addition of my helper.”

    Beulter acknowledged that there are “amazing programs and even governments that care about young people” but added “the people that most, I believe, know or are going to err on the right side of the best interests of their child is the parent and what I’m referring to is 11-month-old Charlie Gard’s quest and his family’s quest to fight a disease.”


  9. In the case of Charlie Gard, the dying British infant whose parents are being denied the right to attempt a long-shot treatment despite having a willing doctor and the money to pay for it, there is a hard question and an easy one.

    The hard question is when medical interventions become too extreme and pointless, when illness and death should be allowed to take their course.

    The easy question, whose answer makes the case a moral travesty, is who should decide the hard question: doctors and judges, or Charlie’s mother and father.

    Much of the confusion around the case reflects a mistaken leap between the two questions. Because the first one is so difficult, some people intuitively assume, the second one must be complicated too. Because one can doubt the wisdom of the parents’ desired course — they have raised over a million dollars to pay for a treatment never attempted with this exact condition, for a child whose brain may have suffered irreversible damage — one must accept the possibility that they should be overruled by Charlie’s doctors and the courts.

    This leap is dangerously mistaken for several reasons. The obvious ones first: The rights of parents are essential to a free society’s architecture, and fathers and mothers are far more likely than any other party to have their child’s best interests close to heart. To intervene on behalf of experts against the family is sometimes necessary but always dangerous, fraught with totalitarian temptations to which the modern West is not immune.

    There is no sign that such intervention is necessary in this case. Trying one last-ditch treatment at an American hospital may be futile, but it’s hardly outrageous — and indeed it would be no more outrageous if the Gards had raised money to take their dying son on a pilgrimage to Lourdes or to some New Age site. To overrule the parental judgment on how to handle an infant’s looming death should require not merely disagreement but real evidence of cruelty or incapacity — something nobody claims is present with the Gards….

    There is, yes, a great deal of costly overtreatment in Western medicine. But there are also countless diseases where progress is agonizingly slow or nonexistent, a myriad of conditions where the official wisdom might be as mistaken as federal diet guidelines always prove to be, and many mysteries that medical science for all its genius has not solved.

    Anyone who has watched a friend die young of cancer, who has battled with a chronic illness, or who has been touched — like the Gards — by a disease too rare to be adequately studied, knows that in the worst of medical situations an expert consensus only takes you so far. In the end you alone have to decide, on information at once imperfect and personal, in the knowledge that all your choices may be bad. And in this dark territory it is not expert confidence but a mix of hope and desperation that leads to breakthroughs and to cures.

    An extra treatment for poor Charlie Gard will probably not lead anywhere. But if a cure is someday found for his condition, it may well happen because somebody, or a succession of somebodies, tried things that the experts said would never work.

    It is for that future’s sake, as well as for the sake of their rights as Charlie’s parents, that the Gards should be allowed to try one last time to heal their baby son.


  10. If there's one thing that has marked the struggle of Chris Gard and Connie Yates, the parents of Charlie Gard, it is the almost inhuman indifference to the plight of the parents by the Great Ormand Street Hospital, who insist that the parents should have no hope of improvement in their son and acquiesce in his death.

    The latest outrage by the hospital is incomprehensible. At a hearing in the family division of Great Britain's High Court, attorneys for the hospital presented the judge with the latest scan of Charlie's brain. But the hospital had failed to share the scan first with Charlie's parents. This proved too much for them and they stormed out of the courtroom.

    Gard’s father yelled “evil” after a lawyer representing Great Ormond Street Hospital broke the news that a report on a new scan on Charlie made for “sad reading.” And Charlie’s mother burst into tears as attorney Katie Gollop told the judge that hospital officials had a negative view of the new scan.

    Justice Francis was analyzing preliminary issues at a hearing in the Family Division of the High Court in London on Friday prior to scheduled trial on Monday.

    Gollop told the judge that doctors had produced a report on the newest scan and said: “It makes for sad reading.” Then Charlie’s mom began to cry and said: “We haven’t even read it.”

    Chris Gard yelled “evil” and added: “I’m not f****** listening to this biased s— anymore.”

    The couple then stormed out of court and then the hospital attorney apologized.

    It's clear from this incident that the hospital, and the British nationalized health service, no longer see Chris Gard and Connie Yates as Charlie's parents. Charlie's life now belongs to the state. Parents are superfluous in this case. They only get in the way...

    Just to make clear, the NHS would not be out a penny if the transfer were made. Charlie's parents have raised the money to bring him to the US.

    Then why the resistance?

    I've pointed this out before but it bears repeating. To the hospital bureaucrats, this is not about life or death. This is about winning or losing. In their bureaucratic wisdom, the hospital has decided that Charlie must die. To carry out that bureaucratic directive is of paramount importance. The parents don't count. The US Congress granting Charlie residency doesn't count. The money doesn't matter.

    Not sharing Charlie's brain scan with those primarily responsible for the baby's well being - the parents - is a clear signal of who the hospital believes has control over Charlie Gard.


  11. With tears streaming down their faces, the parents of terminally ill baby Charlie Gard on Monday withdrew their application seeking to take the child to the United States for an experimental medical treatment, with the couple's lawyer announcing "the window of opportunity has been lost."

    Lawyer Grant Armstrong said at London's High Court it was too late for the 11-month-old child to receive treatment. Recent medical tests revealed Charlie has irreversible muscular damage.

    "It's too late for Charlie," Armstrong said. "The damage has been done"

    Charlie's parents, Chris Gard and Connie Yates, cried in the courtroom as the lawyer announced the news -- their last bid to seek permission to take their child to the U.S. for treatment. Armstrong said the couple now wishes "to spend the maximum amount of time they have left with Charlie."


  12. Mary MacLeod, Chairman of Great Ormond Street Hospital said:

    "Great Ormond Street Hospital cares for many thousands of seriously unwell children every year, providing outstanding treatment for those who need it most.

    Charlie Gard's case is a heart-breaking one. We fully understand that there is intense public interest, and that emotions run high.

    We recognise the tireless advocacy of Charlie's loving parents and the natural sympathy people feel with his situation.

    However, in recent weeks the GOSH community has been subjected to a shocking and disgraceful tide of hostility and disturbance. Staff have received abuse both in the street and online. Thousands of abusive messages have been sent to doctors and nurses whose life's work is to care for sick children. Many of these messages are menacing, including death threats. Families have been harassed and discomforted while visiting their children, and we have received complaints of unacceptable behaviour even within the hospital itself.

    Whatever the strong emotions raised by this case, there can be no excuse for patients and families to have their privacy and peace disturbed as they deal with their own often very stressful situations or for dedicated doctors and nurses to suffer this kind of abuse.

    Great Ormond Street Hospital is in close contact with the Metropolitan Police and we will do everything possible to hold to account anybody who is involved in this kind of deplorable behaviour.”


  13. The parents of a critically ill infant in Britain have abandoned their months-long quest to take their child to the United States for medical treatment, their lawyer said Monday at the latest court hearing in London.

    According to CBS News' partner network BBC News, Grant Armstrong, the couple's lawyer, told the court on Monday that the decision had been made to end the legal battle for Charlie Gard's life due to his latest brain scan results and a U.S. expert in his condition changing his stance on the likely success of any treatment he could offer.

    Speaking in court on Monday, Charlie's mother Connie Yates said making the decision to "let him go" was the hardest thing she and her partner had done in their lives, and they said they still believed their son could have lived a normal life had treatment been administered at an earlier stage.


  14. The parents had been fighting court rulings saying their son’s life support should be withdrawn so he could “die with dignity” for months.

    “We are now in July,” noted Mr Gard. “Our poor boy has been left to lie in hospital for months, without any treatment, while lengthy court battles have been fought.

    “Tragically, having had Charlie’s medical notes reviewed by independent experts, we now know had Charlie been given the treatment sooner he would have had the potential to be a normal, healthy little boy,” he said.

    “Charlie has been left with his illness to deteriorate devastatingly to the point of no return.”

    Mr Gard said their long fight had “never been about ‘the parents know best’. All we wanted to do was take Charlie from one world-renowned hospital to another world-renowned hospital, in an attempt to save his life, and to be treated by the world leader in mitochondrial disease.

    “We will have to live with ‘What Ifs’ for the rest of our lives. Despite the way our son has been spoken about from time to time – as if he is not worthy of a chance at life – our son is an absolute warrior and we could not be more proud of him and we will miss him terribly.

    “His body, heart, and soul may soon be gone, but his spirit will live on for eternity and he will make a difference to people’s lives for years to come. We will make sure of that.”


  15. Now that the US doctor in whom so much hope was invested has said it is “too late” for Charlie to be given experimental nucleoside therapy, one imagines it will only be a matter of time before accusations begin to circulate that delays were somehow deliberately constructed by mysterious UK officials. What is certainly clear is that Charlie’s parents believe their son could have led a normal life had treatment been started in January.

    Doctors and nurses at Great Ormond Street manifestly do not deserve the opprobrium that has been heaped upon them. Nor do the lawyers who have acted for the hospital; nor do the judges who have heard the case at its various stages; nor do expert witnesses. Likewise, there can be no justification for the abuse Chris Gard and Connie Yates have received for challenging the advice of the medical profession.

    There are, in due time, lessons in this awful case for the media and for those who use social media to pontificate on matters they know little about and to spread bile against people they know not at all.

    But before any of that, we should think of Charlie and his parents, who did not deserve any of this. And whatever our thoughts on the very public way their tragedy has played out, we should weep for them.


  16. Chris Gard and Connie Yates’ story, on the other hand, reads like something Sarah Palin would dream up to argue against socialized medicine. The parents of not-quite-one-year-old Charlie Gard wanted to pursue experimental, extreme-long-shot treatment in the United States for their son’s almost certainly fatal genetic condition, called mitochondrial DNA depletion syndrome — on their own dime, using more than £1 million in crowdfunded donations. London’s Great Ormond Street Hospital wanted to turn off his ventilator. The courts sided with the hospital.

    The treatment would almost certainly not work, Mr. Justice Francis ruled. (The American doctor doesn’t disagree.) Charlie “can probably experience pain,” he concluded, and ought to be allowed to “die with dignity” — whatever that’s supposed to mean to an unconscious, brain-damaged baby. Charlie’s parents claim the hospital wouldn’t even allow them the dignity of spending his final hours at home, or at a hospice. And those hours now seem to be at hand. On Monday, Charlie’s parents abandoned their legal battle.

    This always struck me as indefensible. And Britain can be a weird place when it comes to certain freedoms that Canadians and Americans consider fundamental. So I’ve been rather surprised at how many people on this side of the Atlantic seem to approve of the hospital’s and courts’ decisions.

    In an excellent piece at Maclean’s, Alheli Picazo argued the case highlights various fallacies in the way we think about illness — the idea that Charlie is “fighting” and thus must be fought for, for example — and suggested his parents would be better off rejecting vanishingly faint hopes, accepting the inevitable and taking comfort in the “quality time” that would afford them.(continued)

  17. (continued)“Those who suggest there is ‘nothing to lose’ in seeking ‘alternative’ treatments are not allowing themselves to see the intangible, irreplaceable (positive) things that remain, all of which they forfeit to follow a mirage,” she wrote. “Yates and Gard are both victims of this dreadful, depressingly common, trap.”

    Of this, I have no doubt. Human beings are lousy at coping rationally with all kinds of things, death most of all. Surely it does not follow, though, that human courts and human governments should be charged with solving the problem. Not to say any British court has misinterpreted any British law — it seems pretty cut and dried, for better or worse — but courts sometimes get things terribly wrong.

    There are few rights more fundamental than the right to raise your own children, absent extraordinary circumstances, and far too often, in all kinds of different ways, the government buggers it up. As such, I’ll even entertain the idea that parents like J.J.’s[mother was allowed to withhold chemotherapy from her leukemia-afflicted daughter, J.J., on grounds she had an “aboriginal right (to) pursue traditional (aboriginal) medicine.” It was shockingly incoherent. No one had questioned that right; the issue was withdrawing chemo. And the alternative quackery being pursued included a distinctly non-Indigenous variety peddled by a much-discredited Floridian con artist. (The ruling was never appealed.)]should be left alone. But when it comes to foregoing high-probability treatments when the alternative is all-but-certain death, I ultimately come down on the side of intervention: give the kid a chance to appreciate or rue the decision as an adult. By the same token, I can’t possibly support intervening to stop parents like Charlie’s from pursuing the most extraordinary and unlikely methods of saving the only life he’ll ever have.

    Those who fetishize Britain’s National Health Service or Canadian medicare don’t like to admit it, but a properly run universal health care system is a ruthless, unfeeling enterprise. It involves telling people the government won’t pay for treatment X, Y or Z because the chances of success simply aren’t great enough to justify the cost to the public, even if the alternative might be death. It puts a price on human life. And while Canada’s health care system could function vastly better than it does, that basic deal strikes me as entirely defensible — just so long as citizens are free to strike out on their own, or on their children’s behalf, if the state isn’t willing to foot the bill. The treatment Charlie Gard’s parents received strikes me as a serious breach of that very fundamental contract between government and the governed.


  18. Terminally-ill baby Charlie Gard is unlikely to be allowed to spend his final days at home with his parents, a High Court judge has said.

    Mr Justice Francis said he will make a decision about where the 11-month-old boy should spend the remainder of his life, tomorrow

    Doctors caring for Charlie at Great Ormond Street Hospital in London said they want to fulfil the "last desire" of his parents, Chris Gard and Connie Yates.

    But they said there are practical difficulties in providing the intensive care Charlie needs outside a hospital, and the judge said the chances of him being able to spend his final days at home are "small".

    Charlie's parents have become embroiled in a fight with doctors over the circumstances of his death, a day after abandoning attempts to persuade a judge to let him travel to America for experimental treatment.

    Mr Justice Francis presided over the dispute at a hearing in the Family Division of the High Court in London and the hearing is scheduled to resume at 2pm tomorrow.

    The judge said the dispute cried out for settlement.

    However he said if a solution could not be agreed he would decide on it tomorrow.

    Barrister Grant Armstrong, who leads the couple's legal team, suggested to Mr Justice Francis that hospital bosses were placing obstacles in Charlie's parents' way.

    "The parents wish for a few days of tranquillity outside of a hospital setting," Mr Armstrong said.

    "The parents had hoped that Great Ormond Street would work with them."

    He added: "The parents' primary position is that Charlie's final days of palliative care ... should take place at the family home."

    Mr Armstrong said Great Ormond Street doctors thought that moving Charlie to a hospice was the best plan.

    But he said the couple felt there was a "brutality" to taking Charlie to a hospice.

    He told the judge: "We struggle with the difficulties which the hospital is placing in the way."


  19. The parents of 11-month-old Charlie Gard are dropping their request for the terminally-ill infant to die at home, a UK court heard on Wednesday.

    Parents Connie Yates and Chris Gard are trying to assemble a team of doctors and nurses who can move Charlie from the hospital to a hospice so they can spend several days with their son before letting him die.

    They will need the High Court's permission to do that. The test will be whether Judge Nicholas Francis is convinced it's in the child's best interest, as British law requires.

    Hospices focus on supportive care in the final stages of illness, and are not usually set up to accommodate keeping an infant in Charlie's condition alive.

    Grant Armstrong, the parents' lawyer, said yesterday that the couple objected to the "brutality" of moving Charlie to hospice, only to have him die shortly after.

    But Armstrong said Wednesday that the family has found a doctor with previous intensive care experience who would be able to oversee a team at the hospice.

    Armstrong said the couple believes they can put a privately-funded nursing care plan in place, which would include some nurses from London's Great Ormond Street Hospital (GOSH), where Charlie is currently being cared for.


  20. Charlie Gard will be transferred to a hospice to spend his final hours, after his parents abandoned a fight to take him home to die.

    Connie Yates and Chris Gard had hoped to take their son, who has a rare genetic condition, home to spend his final hours as their “last wish”.

    But they ran into opposition from Great Ormond Street hospital, where Charlie is on life support, which said that because of the difficulties of providing invasive ventilation at home and the potential for problems, that would not be possible.

    At the high court on Wednesday, they said that they would instead seek to move him to a hospice, hopefully for “a week or so” but the hospital said that even that would require a 24/7 intensive care team at the hospice, which Gosh was unable to source. It has suggested that he should be removed from life support within hours of being transferred to a hospice.

    The judge, Mr Justice Francis gave the parents until Thursday to find a team that could support Charlie for the days they are looking to spend with him at a hospice.

    “Unless by 12pm tomorrow the parents and guardian and Great Ormond Street hospital can agree alternative arrangements, Charlie will be transferred to a hospice and extubated shortly thereafter,” he said.

    He added: “It seems to me the time has come when a decision has to be taken to a very, very sad conclusion.”

    Francis said he envisaged Wednesday’s proceedings being “the final hearing”, in a case which has been going through the courts for five months.

    The details of when the transfer and removal of life support take place were discussed while journalists were removed from the court but earlier, Fiona Paterson, representing Gosh, said in open court that “it should be Friday”.

    After the private discussions on the details had taken place, Yates, shouted:

    “What if it was your child?” and “Hope you’re happy with yourself” before leaving the court in tears.

    Afterwards, an unnamed family friend said: “The hospital have set the bar so high that in terms of clinical team for Charlie’s end of life nothing seemed good enough for Gosh. The reality is Charlie is very stable, not in pain and rarely needs a doctor. It is therefore difficult to understand why Charlie could not die at home. All he needs is a ventilator which pumps room air into his lungs.

    “It is extraordinarily sad that there’s been so much fuss about him dying at home. Connie and Chris have conceded a hospice but it was not their first choice. They will be devastated they have not been granted their final wishes as parents.”

    The family later put a message on Facebook appealing for a paediatric intensive care consultant to come forward before 12pm on Thursday. It said: “Please only email if you can help us! We need some peaceful time with our baby boy.”

    Earlier, Yates’s hopes of being able to take Charlie to the hospice for an appreciable period of time were raised, when her lawyer, Grant Armstrong, announced that a doctor “with experience as a surgeon” in intensive care and who ran a team with a paediatric doctor had offered to oversee his life support at the hospice and was on his way to court.

    However, it later emerged that he was a GP with “no experience of intensive care”, according to Victoria Butler-Cole, the lawyer for the guardian.

    Armstrong also said that several nurses at Great Ormond Street had volunteered to assist in Charlie’s care outside the hospital setting.


  21. On Monday, Miss Yates, 31, and Mr Gard, 33, reduced the High Court to tears by making the agonising decision to let Charlie die after an eight-month legal battle.

    They accepted their 11-month-old, who has mitochondrial disease, was now beyond hope of any cure – which they blamed on 'a lot of wasted time' by medics – and would not live to see his first birthday on Friday next week.

    But their plan to take Charlie home, give him baths and let him sleep in his cot before saying their final goodbyes on Monday next week were dashed by the hospital.

    Great Ormond Street said he should go to a hospice - or stay with them - because his ventilator won't fit through the front door and doctors fear he could suffer pain or a 'distressing or disordered death'.

    A family friend said: 'The hospital have set the bar so high that in terms of clinical team for Charlie's end of life nothing seemed good enough for gosh.

    'The reality is Charlie is very stable, not in pain and rarely needs a doctor. It is therefore difficult to understand why Charlie could not die at home.

    'All he needs is a ventilator which pumps room air into his lungs. It is extraordinarily sad that there's been so much fuss about him dying at home.

    'Connie and Chris have conceded a hospice but it was not their first choice.

    'They will be devastated they have not been granted their final wishes as parents.'

    The judge said life-support treatment would end shortly after Charlie arrived at the hospice.

    Grant Armstrong, who led Charlie's parents' legal team, said the couple wanted to privately fund care at a hospice where Charlie could continue to receive life-support treatment for days before being allowed to die.

    He said a doctor was ready to help and several Great Ormond Street nurses had volunteered their services.

    Great Ormond Street bosses said they were not satisfied that a properly-qualified specialist would be in control under Charlie's parents' plan.

    A lawyer in the couple's legal team said discussions about mounting an appeal against Mr Justice Francis's decision not to allow more time were taking place.

    Mr Armstrong said a firm had offered to 'provide any type of ventilator that is required.'

    Two nurses would be needed for each shift lasting eight to 12 hours and GOSH staff have volunteered to work on their days off or between shifts at the hospital.