267 pointsby Shortness86 hours ago29 comments
  • maxall44 hours ago
    I'm honestly quite shocked that the physicians/scientists involved would choose to use an AAV for a brain-targeted gene therapy. There is just so much data demonstrating that these vectors are quite immunoreactive: most of the approved gene therapies based on AAVs carry black box labels for liver failure caused by an immune reaction to the viral capsid. Admittedly, AAVs are the most derisked vector for gene therapies, but infusing them directly into someone's brain and expecting nothing bad to happen is, in my view, crazy.
    • timy2shoes2 hours ago
      Another compounding issue is that they had to package the vector into two parts, which then have to both infect the same cell to get any effect. Which means you have to at least double the dose to get similar coverage compared to a single AAV vector (and actually more than double). Seems like a easy recipe for liver toxicity. Which is why most companies doing AAV therapy either target the liver or the eye (where AAV doesn't escape to the liver).

      I feel like the parents were not well enough informed of the risks, and the PI rushed the therapy to be famous. Not the first time this has happened, and not the last, sadly.

    • gus_massaan hour ago
      IANAMD. I remember something about that virus in the brain are super bad, and there is an additional protection to avoid virus and random substances entering the brain. They injected the virus in the medula, that is inside the protection membrane. In an ideal case, is it a good idea?
  • senderista4 hours ago
    Many years ago I was attending pre-surgery for a hip replacement surgery for my sister, who had known severe reactions to anesthesia (actually required a tracheotomy for a previous reaction). The anesthesiologist asked to speak to us privately and informed us that in their opinion, my sister had maybe a 1/3 chance of not surviving the surgery. They also mentioned that this was a breach of protocol and they could get in trouble for talking to us directly, but their conscience wouldn't let them do otherwise. We returned and asked the surgeon if they really thought the risk justified any potential benefit. The surgeon shrugged and said "probably not, feel free to call it off". Keep in mind that nobody on the care team had previously discussed any risk or indeed any tradeoffs whatsoever. This was at one of the best-regarded children's hospitals in the USA.

    The lesson for me is that you must advocate for yourself and your loved ones in the medical system, because doctors will not do it for you; they may not even perform the most basic risk assessments. And you have to try to quantify risk yourself, because doctors will refuse to give you the slightest hint of any number attached to risk (I know, I've tried many times).

    • itishappy3 hours ago
      > The lesson for me is that you must advocate for yourself and your loved ones in the medical system, because doctors will not do it for you; they may not even perform the most basic risk assessments. And you have to try to quantify risk yourself, because doctors will refuse to give you the slightest hint of any number attached to risk (I know, I've tried many times).

      Doctors vary wildly, and that's part of the issue. For instance, my oncologist had zero problem rattling off mortality statistics. I've personally had doctors try to sell me surgery before identifying the issue, but I've also had doctors successfully talk me out of what would have been useful procedures by offering their risk/benefit assessment unprompted.

      It's like any other field. If there are 10x and 0.1x engineers, you bet there are 10x and 0.1x doctors. A 1hr intake appointment isn't anywhere near enough time to judge even for folks in the field.

      • thruway5153 hours ago
        No it's not like any other field. There's no such thing as a 10x doctor. A '10x' doctor is just as likely to kill you as any other especially when it comes to experimental never before done procedure. In fact a 10x doctor like Qiu is more likely to take risks. This is medicine not a software shop where we measure productivity by number of commits or number of surgeries per hour except by 10x you mean 10times more likely to be careful and ethical
        • exmadscientist2 hours ago
          I think there absolutely are 10x doctors! When every doctor or specialist you meet in a field says "yeah, Dr X is a massive asshole and I kind of hate him personally but if I ever need [not-particularly-rare procedure Y], I want him to be the one to do it", I think Dr X counts.
        • itishappy2 hours ago
          Yeah, I don't mean it literally, nor do I necessarily agree with the concept of 10x engineers in general, but it's a useful shorthand. I would bet doctors vary somewhat less than other fields, but my family has been surprised and burnt by the variance still there, and I'm the only non-doctor!

          On the topic of 10x surgeries per hour, the 1800s were an interesting time! This guy in particular:

          https://en.wikipedia.org/wiki/Robert_Liston

        • nickff3 hours ago
          What exactly do you mean by "10x doctor"?

          Some surgeons have a 10x higher 'revision rate' than others, and from what I understand, that may be an understatement. Many of the statistics which would indicate the ones to avoid are not tracked, precisely because the doctors do not want them tracked.

          • thruway5152 hours ago
            You'll have to ask the OP what they meant by 10x. I assume they meant it in the programmer/hacker sense of producing more work in the same amount of time than their peers or being a 'rockstar'
            • solumunus15 minutes ago
              Obviously they simply mean highly talented compared to their peers.
        • foco_tubi2 hours ago
          The point is, there are excellent doctors, good doctors, bad doctors, and awful doctors who should probably have their licensure revoked; just like engineers, or any other profession, there is a spectrum to the quality of service/talent/care.
      • antisthenes21 minutes ago
        > If there are 10x and 0.1x engineers, you bet there are 10x and 0.1x doctors.

        So if we already have a massive doctor shortage, including 0.1x doctors, you can begin to guess how awful the medical system is in the US.

        You could be paying exorbitant rates only to end up with a 0.1x doctor, because there was literally no one else within 30 miles in a rural area.

        Pretty depressing to think about.

      • ButlerianJihad2 hours ago
        https://youtu.be/6h6dhevlb0w?is=t-cLAwe5vBuKx_fZ

        Your Coworker Who's a 10× Engineer

    • genericresponse3 hours ago
      This seems very unusual on many, many levels. I hate to ask, but were you a child when this happened? If so, are you sure you were in all the conversations. First- There are less than 600 total hip replacements conducted each year on children in the United States. Second- It would be unusual for this surgery to be even recommended without something serious being addressed. Third- Failure to discuss risks and tradeoffs would be regarded as malpractice if something went wrong.
      • 2 hours ago
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    • Loughla4 hours ago
      The problem is, how do you know when to advocate for yourself?

      I have zero idea if what the doctor is telling me is accurate or not. I'm not a doctor.

      This is why people are moving away from main stream medicine, in my opinion.

      • RobotToaster3 hours ago
        "do your own research" may get mocked, but it's often the best strategy. You just have to make sure it's the right place, professional guidelines, pubmed, and anyone referencing those is usually best. A good doctor won't have issues discussing something from that kind of source.
        • jimbooonooo2 hours ago
          respectfully, a majority of the "do your own research" crowd are not reading any PubMed or professional guidelines.
      • snaking07763 hours ago
        Having dealt with the medical system recently, if there isn’t immediate harm involved with waiting, always advocate for yourself and consider a second opinion. The doctors will think you’re annoying and that you trust the internet too much but it’s their job to make you understand why elective procedures are necessary. Don’t let someone trying to rush to their next patient hurt your health outcome. I think in emergency situations this all changes though.
        • jcul3 hours ago
          During my wife's second pregnancy, we got a lot more information and did more preparation than for the first.

          Someone shared the BRAIN acronym for making decisions.

          Can't remember it exactly, but it was like ask / think about benefits, risks, alternatives, intuition, doing Nothing (for now).

          I think the Nothing one was the most important, what happens if I don't take action and defer the decision. Medical professionals often make you feel like a decision is urgent when sometimes it is not.

          • snaking07762 hours ago
            I like that rule. I’ve also found that for most things that are risky enough to warrant a second opinion it will probably take long enough to get in that you can schedule it several months in advance and then use the intervening time to learn more although calling medical offices to schedule appointments is no fun.
      • ipaddr3 hours ago
        Always advocate and avoid delegation to experts who have little stake in the outcome.
        • iambateman3 hours ago
          Parent had a good question and this is restating what’s already been said.

          _how_ do you advocate? If I could avoid delegating to experts, I wouldn’t be in the situation in the first place.

      • nkrisc3 hours ago
        How is it any different for non-mainstream medicine? How do you know if what your homeopath is telling you is accurate?
      • outworlder3 hours ago
        > This is why people are moving away from main stream medicine, in my opinion.

        What other type of medicine is there? Most "non-mainstream" things are pseudoscience nonsense.

    • tomcam2 hours ago
      > Keep in mind that nobody on the care team had previously discussed any risk or indeed any tradeoffs whatsoever. This was at one of the best-regarded children's hospitals in the USA.

      I bet you live in the Seattle area. Similar experience with my daughter.

    • diskzero3 hours ago
      That is terrible and I am glad someone broke ranks to inform you of the risk.

      My wife had a very agressive triple-hit lymphoma and CAR-T was eventually suggested. Fortunately, the medical team was very honest about how hard it impacts your body, with very likely chance of death. My wife decided to do it, and it almost killed her. The team actually had to "shut down" the process, so she didn't benefit completely from the treatment. The suffering was pretty immense as well. She died a few months later regardless.

      We are (were) both engineers and we did wonder how many might get streamrolled by the whole medical process, where you do get this odd combination of extreme indifference and optimistic exuberance.

      • esotericrunner3 hours ago
        Sorry for your loss, I feel your pain. Your wife was very brave to give it a shot and take the fight to the limit, and you should remember her courage and honor her memory and keep fighting till the end regardless of what hardships you encounter in life.

        The treatment actually killed my dad. I may be wrong but it appears with the treatment there was a 30% chance of some recovery, 40% chance that it would at least stop the cancer growth, 30% chance that it had no impact. I guess you have to take that chance when you have no other option. I don't blame the hospital (which was terrible) or the treatment, it was the last card left. And our loved ones end up in the 30% statistic and maybe as another anecdote for the risks section, but we know what we they went through and we won't forget.

        It was tough because my dad was suffering, but he still was active and had at least a few months left without the treatment and I know that at that point in his battle he did this treatment to keep fighting for us rather than for him, even though it was he who had to suffer through it. So I am going to honor his memory and keep fighting until the end as well.

    • al_borland3 hours ago
      I think this is how they avoid liability. They lay out some options and leave it up to the patients, with no medial training, to decide how they want to move forward.
    • nkrisc3 hours ago
      You’re absolutely correct, but I think your story about the anesthesiologist shows that there are some doctors who do care.
    • ekianjo3 hours ago
      Most doctors are very bad at data as well. Few understand statistics. That does not help.
    • api4 hours ago
      US healthcare is very strange in that on one hand it pinches pennies and is incentivized to not fund treatment, but on the other hand there seems to be some kind of internal incentivize to spend liberally and do everything.

      The whole system is a mess of perverse incentives. I've often described it as "everything bad about socialized medicine combined with everything bad about privatized medicine."

      • modeless3 hours ago
        Some people thought it was a good idea to cap [administration cost + profit] of health insurance companies as a percentage of premiums. As a result, health insurance administrators have two ways to increase their compensation: they can compete to acquire more customers, or they can artificially inflate costs per customer. Guess which one is easier! Now you don't have to wonder why medication is half the cost when you buy it without insurance...

        Love to hear all the time how the "free market" is ruining healthcare. Of course everyone knows a "free market" is when you have profit caps, supply restrictions (residency cap), government-run marketplaces, byzantine tax subsidies tying insurance to employment for no reason, etc etc

        • Avicebron3 hours ago
          If anyone is curious, this the USA, it came from the ACA in 2010 championed by Democrats. It's almost like it doesn't matter which jersey is being worn.
        • api2 hours ago
          That's what I meant. It's over-regulated and sclerotic, criticisms often levied at socialized medicine, but is also unequal, expensive, and excludes many people. So it's like everything that sucks about socialized medicine without the upside.
        • Eisenstein3 hours ago
          > Love to hear all the time how the "free market" is ruining healthcare. Of course everyone knows a "free market" is when you have profit caps, supply restrictions (residency cap), government-run marketplaces, byzantine tax subsidies tying insurance to employment for no reason, etc etc

          What people are talking about with regard to health insurance being ruined by being market based is that the profit motive should not be applied to it. The basic fact is that it should be some form public service and not reliant on a system which has as its incentive maximizing profits, and attempting to regulate it into being patient first and not profit first will always have side-effects like you pointed out.

          • modeless3 hours ago
            Removing the "evil" profit motive has always been an argument for socialism. If it would work for healthcare, why not everything?
            • api2 hours ago
              Steel man counter-argument: health care is weird and different and special in lots of ways.

              The people who need it most are often the least profitable to treat and the least able to pay for it. That's because being sick negatively impacts your earning potential. The sicker you are the less you can afford a way to pay for treatment to not be sick. It's analogous to the problem with debtors' prison.

              Obscure or low-survival-rate conditions are almost by definition unprofitable to treat. Rare condition? Stage four cancer? It's most profitable to let you suffer or die. There's not enough of a market for the former and the latter has a low probability of leaving someone behind to pay the bill.

              Old age care can't be profitably offered on insurance or credit. Old? Pay cash or die.

              Demand is not infinite because (excluding certain neuroses) people generally do not want health care. They only get it when they need it. Demand does not skyrocket with reduced price or free availability, so the system doesn't automatically just drown in demand when you take the cost away.

              Competition is sparse because talent is scarce and the cost means there tend to be only one or a few hospitals covering an area. Specialty services and general practitioners are different, but for advanced and expensive care it tends to be not quite a natural monopoly but almost one. It's like how there's not very many space launch companies. Because it's so f'ing hard the supply of competitors is small.

              Lastly, because customers are ignorant (very few people are qualified to evaluate health care tech or treatments), quackery is structurally more profitable than medicine that works. It's hard to have a healthy market when fraud is massively easier and more profitable and the customer finds it hard to tell the difference. Add to that the fact that try before you buy and comparison shopping are almost impossible, especially for serious medical care. You can't exactly toss out or return a surgery.

        • qotgalaxy2 hours ago
          [dead]
      • alightsoul4 hours ago
        This is what happens when healthcare is for profit.
        • 3 hours ago
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        • m0llusk3 hours ago
          It is more complicated than that. Markets have the structure and regulations we give them. Health care gets set up and delivered with very different concepts and guidance in various places regardless of whether it is for profit.
          • laughing_man3 hours ago
            We don't have a true free-market in health care, so regulations and various programs are meant to create an environment where we get the benefits of a free market while still having universal availability and a universal "standard of care".

            Of course it doesn't work very well. That's asking too much of any system.

          • alightsoul3 hours ago
            How is not weighing risk not for profit, when not weighing it is crucial for profit?
    • HedonicEscal8r4 hours ago
      Malignant hyperthermia?
    • caraffle4 hours ago
      This is fear mongering at best and unbelievable. Why would a surgeon know anything about anesthesia risk? Anesthesia regurarly cancels cases due to safety concerns - there's no "protocol" or "getting in trouble" (what does that even mean), that's standard of care. "Anesthesia" is a doctor too and ultimately holds the call on if they will put a patient under or not.
      • Supermancho3 hours ago
        This is matches my experience, having been under at least 30 times.

        The phrase:

        "Why would a surgeon know anything about anesthesia risk?"

        could be misleading to someone who has never undergone (or just didn't understand) what a pre-surgery anesthesiologist consult is for.

        Surgeries are performed by teams. Anesthesia is one aspect of the procedure and most of the doctors know some, while surgeons know a great deal. The anesthesiologist's job, as a physician, is to monitor, adjust, and assess risk during the procedure. This disclosure, if it happened, was during the consultation.

      • amatecha3 hours ago
        > Why would a surgeon know anything about anesthesia risk?

        Idunno, maybe because their entire career is performing surgeries which include anaesthesia and they have worked for potentially decades alongside anaesthesiologists? For instance, I've worked in the same type of role (programmer) for my entire career and I somehow know a ton about the disciplines adjacent or closely related to mine, especially because I work with them every day.

        • Supermancho3 hours ago
          Graciously, I think this was the point they were trying to make, with an inappropriately sarcastic intro.
        • solenoid09373 hours ago
          Medicine is not programming.
      • Georgelemental3 hours ago
        "Anesthesia" could also be a nurse anesthesist, nurses generally aren't supposed to contradict doctors in front of patients
    • esikich3 hours ago
      I don't believe this for a second. The anesthesiologist is obligated to tell them this, they meet and discuss this kind of thing with the family/patient. It isn't a breach of protocol, the doctor and surgeon would also have been informed and would have relayed as well.

      Fear mongering bullshit.

      • HedonicEscal8r3 hours ago
        I agree, sounds suspicious and likely misremembered.
  • lconnell9625 hours ago
    An article about the complicated issue that is a child with a non-lethal developmental disorder getting a treatment that ends with the tragedy of the headline. The article might be sensationalizing the situation, but it makes the doctor out like a monster and as the facts read I can't say I disagree.

    That the treatment was inconclusive in the animal studies isn't particularly shocking. The brain is one of the more complicated parts of a human body after all. Ethics and safty concerns seemed to get ignored all the way to the actual treatment speaks like the money and potential fame was all the medical staff involved were concerned with. The parent's aren't blameless, they wanted to fix a child who probably would have lived with a below average quality of life. The article claims they were mislead to believe this treatment was safer than it actually was.

    The treatment vehicle seems like the cause of death as reported toward the end, but there are words about the animal testing that imply this could have been a known risk with the treatment as a whole. The number of things being found with hindsight remind me of "move fast and break things" development. It really sounds like cutting edge (bio)tech has ethics get ignored when money and fame are on the table.

    • 4 hours ago
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    • throwway1203854 hours ago
      I didn't read it as making the doctor a monster. What I saw in the story is an example of how the road to hell is paved with good intentions.
      • ndiddy4 hours ago
        He's pretty clearly a monster or at least monster adjacent. He and his team

        * Took hundreds of thousands of dollars under the table to develop the treatment

        * Neglected to take steps that would determine whether the treatment was safe to use on humans

        * Didn't inform the family that the treatment could possibly kill their daughter

        * After the treatment did kill their daughter, he published the study anyway except stripped of any mention of the failed human trial and of any negative side effects caused by the immune system reacting to the virus

        The most generous interpretation of this is that Qiu and his team were racing to be the first to cure a mental disorder using gene editing and neglected to take the necessary safety precautions, but that still makes him a horrible person because it resulted in the unnecessary death of a child just because he was hoping to be first. I'm glad the parents decided to go public about this (especially since they must feel devastated about their daughter's death) if it means he won't get to try the same risky procedure on other children.

        • ElProlactin4 hours ago
          > Didn't inform the family that the treatment could possibly kill their daughter

          From the article:

          > The parents had heard about serious side effects, including deaths, caused by other gene therapies, and knew the greatest risk would be Mei’s immune response to the massive dose of virus. Qiu said getting the dose right was critical, but infusing the viruses directly into Mei’s spinal fluid, rather than the blood, would minimize the threat of a reaction because it would bypass the kidneys and liver.

          The article paints a picture of well-educated parents who were incredibly focused and dedicated to their "mission", which was basically to "cure" their daughter's condition using gene editing, something that had never been done before. They participated in groups, recorded the conversations with the doctor and ostensibly did enough research to have concerns in the first place.

          The doctor violated every ethics rule in the book and should never be allowed to touch another human being, but I don't think it's fair to pretend that the parents were unwitting.

          • ndiddy3 hours ago
            Right, part of his whole pitch was that he had a new cutting edge gene therapy that was more precise than CRISPR. I think the parents were definitely obsessed with "fixing their daughter", but it seems like Qiu didn't try at all to "snap them out of it" by mentioning how the treatment he was attempting could also kill her.
            • ElProlactin3 hours ago
              Of course he didn't try to discourage them. He wanted to do this type of research/experimentation, which is almost certainly why he was known to the communities the parents were a part of (the article says the parents learned of him in a "WeChat group in which parents of children with autism and similar disorders trade advice").

              This is a form of doctor shopping. If you really want something, you can find someone who is willing to provide it, even in fields like medicine where practitioners are expected to adhere to rigorous ethical standards.

        • mft_3 hours ago
          > * Took hundreds of thousands of dollars under the table to develop the treatment

          I'm in two minds about this.

          On the one hand, at face value the funding and payments seem dubious - especially with the mention of one of the doctors returning his payments, suggesting they were for his personal enrichment, rather than payment for the costs of the treatment development and trial.

          On the other hand, the parents were literally funding the creation, for the first time ever, of a highly complex treatment essentially custom-made for their daughter's condition. This required a lot of detailed and expensive science, with the generation of a mouse model of the disease, followed by development of the treatment, and then the testing of this in monkeys. In US/EU, this work would likely cost millions of dollars/euros, and it's not unreasonable that it would also cost a significant sum of money in China.

          • altairprime38 minutes ago
            Her distinctiveness has been added the collective. That's what experimental medicine is for! So if you approach this story from an amoral "ethics-free" standpoint (which is easy for me but, thankfully, difficult for most) their money has technically benefited human science, however problematic the circumstances. I have some serious glee at seeing the quantity of moral output being generated in this discussion. HN's culture is largely Bay Area tech, which has also been a key innovation driver in ethics-free amorality such as Meta and Theranos. May our own reflection in this medical science funhouse mirror encourage us to express such intense moral and ethical concern at not only our tech social media site HN, but more importantly at our often-amoral tech workplaces as well.
          • solenoid09373 hours ago
            Yeah, I was also surprised by how inexpensive this was.
        • decimalenough3 hours ago
          If he had succeeded, though, he would have been a hero, both to the parents and the world. And the same racing that we are condemning as monstrous would have saved other children as well.

          Obviously I'm not saying he is a hero or that what he did is right, just pointing out that the ethical tradeoffs in medical research like this get very complicated very fast. Ultimately it boils down to the trolley problem: is sacrificing a few worth saving many others?

          • 0dayzan hour ago
            Not exactly, trolley problem is about a sacrifice, in this case the idea is no sacrifice, because failure is absolute, especially in that you gain nothing, Quis research is as useless to cite as Dr He, yes they both used certain scientific approaches, but clearly skipped medical and ethical concerns.
          • MSKJ3 hours ago
            It doesn't seem like success was of particular import to the doctor, rather the goal seems to have been to get a 'test subject'
        • ButlerianJihad4 hours ago
          > monster

          > monster

          > monster

          Perhaps if his genes were properly modified, then he could become nearly human in the court of public opinion.

    • taurath4 hours ago
      > The number of things being found with hindsight remind me of "move fast and break things" development.

      It is the same mentality in all of business rn, everyone is ruthless and doesn’t give a single fuck about consequences because they won’t be coming for another 2 years at least and people have a short memory

      • PearlRiver4 hours ago
        Also if you have a few hundred million bucks you will still have your mansion if you get it wrong.
    • streetfighter644 hours ago
      > It really sounds like cutting edge biotech has ethics get ignored when money and fame are on the table.

      Wouldn't be the first time. Nor the first time the actual evidence of effectiveness of the treatment (i.e. even when working as intended) was ignored.

    • micromacrofoot4 hours ago
      Wealth can override pretty much anything; ethics, decency, common sense. This is a lesson humans have had thousands of years and countless examples to learn from and still haven't managed.
    • 395trek4 hours ago
      kinda sounds like in vivo test driven dev
  • fabian2k5 hours ago
    There's so many ethical problems with the events as described in the article. The worst to me seems to be that the researchers/doctors seem to have downplayed the risks here. Which for a never before tried gene therapy that is meant to work inside the brain are absolutely enormous. The ethical issues around the money seem minor in comparison with that and the fact that they seem to have ignored similar side effects in the monkey experiments.
    • cowlby5 hours ago
      Reminds me of the TGN1412 drug trial where patients had severe immune reaction and almost died. Sad that the story suggests they ignored all the signs that would suggest humans would have a bad immune reaction to it and proceeded anyway.

      https://www.reddit.com/r/Documentaries/comments/jrraz7/when_...

      • mft_3 hours ago
        With TGN1412, it wasn't that the right work wasn't done, or that results ignored, but rather that the regulations in place at the time weren't right to deal with that sort of drug. Following what happened, the regulations were changed around the world to be more cautious and suitable.
    • trollbridge5 hours ago
      I’m very puzzled why this wasn’t replicated in eg a study in rats first (where you duplicate the mutation, and then attempt to cure it).
      • austin-schick5 hours ago
        The article says that they did do this:

        > Qiu’s team had engineered mice to have a human version of the CHD3 gene with their daughter’s mutation, R1025W, which results in a protein with the amino acid tryptophan where there should be an arginine. The mutant pups developed autismlike traits and didn’t squeak as much as normal mice when separated from their mothers. When the researchers repaired that mutation, the pups developed normally.

      • fabian2k5 hours ago
        They did animal experiments first. But according to the article they didn't really look at the serious side effects observed in monkeys, or ignored them. But animal experiments can only provide warning signs here, they can't tell you what will really happen in a human.
      • 4 hours ago
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      • 5 hours ago
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  • Terr_5 hours ago
    > The paper had an enthusiastic reception. “These promising results might pave the way for the development of an effective clinical treatment,” Kevin Bender, a neuroscientist at UC San Francisco, wrote in an accompanying commentary. At the time, Bender had no idea that a girl had received it and was already dead. Meanwhile, Chinese state media, CCTV, called the work “the first ray of hope” for “countless families suffering such diseases.”

    Oof, there's something deeply unjust about that, a kind of "adding insult to fatality."

    People celebrating that a new treatment will save children and give hope... with no acknowledgement that it was just tried and cost you both.

    • streetfighter644 hours ago
      Sounds extremely similar to the first victims of Macchiarini. He and his entourage were writing and publishing success stories about his experiments when the victims had already died.
    • drekipus5 hours ago
      "Millions of deaths don't matter if we can save just one." is an increasingly common take.
      • cucumber37328424 hours ago
        If you really want people to fall for the like you put fractional life on one side of the equation and whole numbers of life on the other "millions of people ought to toil for untold millions of man hours totaling to hundreds of lifetimes to save a few lives" and all that.
  • Shitty-kitty4 hours ago
    It is important to note that in China, developmental delays are treated with ridicule for the affected and as a source of shame for the families.

    I'm not passing judgment on the parents, I'm just pointing out that how society treats developmental delays is extremely important to the quality of life of these people.

    Here in the US autism was considered a "mental illness" until the 1980's.

    • jwrallie2 hours ago
      I think this is an important nuance that may be missed in the article. The teacher pulling the parent aside to ask her to check her child made me remember what my partner said about the time they moved to China as a kid and how they were treated in school because they were falling behind their peers. (In that case because they couldn’t keep up with the natives due to language skills.)

      I too do not mean this particular teacher is to blame rather than the way society works.

  • 1saadcodes3 hours ago
    Cases like this are heartbreaking, but they're also a reminder that failures like this ones need to be published just as prominently as success. Gene editing is still a young field, and if negative outcomes remain hidden, other researchers can't properly assess risks or make improvements
  • HedonicEscal8r4 hours ago
    There are many children with life-threatening rare diseases that would be much better candidates for risky experimental treatment like this. Very sad case.
  • throwaway898643 hours ago
    Here are some illustration of people living with this disease:

    https://en.wikipedia.org/wiki/Snijders_Blok%E2%80%93Campeau_...

  • wnevets5 hours ago
    > When Mei was 4, one of her kindergarten teachers pulled Linda aside: Mei didn’t draw or write as well as the other kids and her language skills weren’t developing normally. Her mother might want to get her evaluated, the teacher said. In March 2023, Mei was diagnosed with global developmental delay, a broad label with many causes. Specialists explained that some of Mei’s behaviors—the funny sounds she liked to make, for instance—were associated with autism.
    • ToucanLoucan5 hours ago
      It says so much about how our society treats the neurodivergent that it's considered a non-extreme opinion that a dead child is preferable to an autistic one.
      • elictronic4 hours ago
        Pretty sure the parents weren’t expecting a 50-50 shot of cure vs death. The medical staff downplaying risk and ignoring issues seems like the bigger problem especially for a developmental procedure. If they represented the risk as 1 in 10000 I would probably take those odds. If the actual risk was 1 in 5 and they didn’t convey that it’s pretty messed up.

        Getting in your car has risk, so does riding a bike. They shouldn’t be coin flips.

      • CuriouslyC4 hours ago
        You should try being the parent of a seriously autistic child. I'd put a large chunk of cash down that most parents of severely autistic children wish their child had never been born. There's no upside, it basically ruins your life. Every interaction is a reminder of what you will never have, and what you will have to suffer through for the rest of your life.
        • fwip4 hours ago
          If you really feel this way, get some therapy. The only one ruining your life is you.
          • numeri4 hours ago
            This is a terribly unempathetic response to someone opening up about a very taboo (but probably very common), painful emotion they've experienced.
          • CuriouslyC3 hours ago
            If you think I'm the one ruining my life, having to change diapers and do most everything for someone who can't talk, has limited motor skills so he has to be pushed around half the time rather than walk anywhere, who needs constant attention, and will probably need constant attention for the rest of his life, your "wokeness" has lead you to be incredibly cruel.
      • orangedog4 hours ago
        That's not what happened here. The team was too ambitious and not careful enough but they were not trying to kill the child.

        I just don't think there is any reason to put that additional context into what happened here.

        • ryandrake4 hours ago
          I think what OP was trying to ask was why would a parent be willing to put their child at lethal risk, using an experimental treatment, for a condition that itself is not lethal? I don't have a kid with autism or a learning disability so I don't know how I'd handle it, but if I did, I'd probably choose to live with it and help the child make the best of it. I would not be reaching for someone's research project.
          • mparkms4 hours ago
            It does not sound like the possibility of death was properly conveyed to the parents.

            >But nowhere did the form explicitly indicate that any of this could end in death, nor did that come up during any conversations with Qiu or the other doctors, Jason and Linda say.

          • sokoloff4 hours ago
            Parents put their children at lethal risk (albeit small) for non-lethal conditions all the time.

            Wisdom teeth removal under general anesthesia is around 1 in 100,000.

            It doesn’t sound so crazy if the risks were presented as “only 10x as risky as wisdom teeth extraction”.

            • XorNot4 hours ago
              I don't know where you're getting that number from. For all dental anesthesia the risk rate seems to be literally 1 in a million [1] and the various law firms which popped up during that search suggested better then 1 in 300,000 at least.

              Which also omits the base level mortality of dental complications wisdom teeth are likely to cause.

              [1] https://pmc.ncbi.nlm.nih.gov/articles/PMC5535496/

              • sokoloff4 hours ago
                Table 1 in your link does not support 1 in a million for general anesthesia procedures, unless I’m badly misreading it.

                Nor does the discussion section nor overall summary figure, which is 3 in a million for all forms of anesthesia (local, sedation, and general), where you have to at least exclude local anesthesia (the most common type) as having a fundamentally lower risk of death than sedation or GA.

          • elzbardico4 hours ago
            People without extensive scientific training can be easily convinced by an un-ethical expert that the risks are negligible.

            That's why we need external controls, ethical commites and so on.

          • Mezzie4 hours ago
            In this case, you're probably right, but there are definitely spaces between 'live with it' and 'lethal'.

            I have multiple sclerosis and at the time of my diagnosis the best treatment available to me in terms of slowing the progression of MS had a risk of triggering a rare brain infection that would kill you. So it was a choice between treatments that didn't work as well but had lower risk and treatments with greater odds of being able to walk/work/not be in horrifying constant pain in 10 years but also a small chance of death.

            These decisions can end up being horribly complicated, and they are definitely revealing in terms of your values.

      • tliltocatl4 hours ago
        Neurodivergency, or whatever you might call it, sucks, at least during childhood. Ten times so in a family-centered society. I had a mild enough case to grow up functional and independent, but if not for that… I totally see how one might chose a risky treatment even when fully informed. The problem here, it looks like the consent was nowhere informed enough, and the research team chose not to publish the case after it turned out a failure.
      • Deukhoofd4 hours ago
        The article clearly points out that it wasn't autism for which Mei was treated, but Snijders Blok–Campeau syndrome, of which autism is just a single symptom. That goes way beyond neurodivergency.
      • outworlder3 hours ago
        > It says so much about how our society treats the neurodivergent that it's considered a non-extreme opinion that a dead child is preferable to an autistic one.

        They did not set out to kill the child. And the autism wasn't even the biggest issue. The issue is the developmental delays that were expected to compound the more the brain was left untreated.

      • asa1234 hours ago
        This seems to be a rather extreme takeaway..?
      • slashdave4 hours ago
        It was a genetic disorder. Stop with the silly labeling.
      • 3 hours ago
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      • fwip4 hours ago
        I hear this meme sometimes, that anti-vaxxers and others "prefer a dead child to an autistic one," and I think it fundamentally doesn't represent their thought process at all.

        The far-more common sentiment that I see among anti-vaxxers is that the risk of death from childhood diseases like chicken pox are either zero or close-to-it, and that the risk of receiving autism from the vaccine is at least one-in-ten. These numbers aren't true, of course, but in their minds, they're weighing a negligible-chance of terrible outcome against a moderate chance of bad outcome.

        I'm sure there's a few extremists of course, who would say they prefer a dead child to an autistic one (same as how some parents feel about gay kids), but it does not represent most of the people in these movements.

  • amoorthy3 hours ago
    Two years ago, my then 81-yr old father, who had Progressive Supranuclear Palsy, was recommended to get back surgery to relieve chronic and debilitating pain. The neurosurgeon said it's routine surgery and he's done it on people much older. We ultimately decided against it and found that a simple wedge pillow to sleep on relieved his pain. A bloody $50 pillow. And this came from a recommendation from a physiotherapist.

    What's particularly galling is the recovery from back surgery would've taken at least 6-9 months of rehab and my father's PSP was already sapping his motor skills and yet the surgeon was pushing ahead.

    Even with my mom I've had to intervene on several occasions against the doctor's utterly idiotic ideas. Thank goodness for AI to at least make us conversant to ask the right questions of these doctors.

    • uurrnn2 hours ago
      Physios really are great
      • harry82 hours ago
        Can be. They vary like _every_ other profession.
  • oceansky5 hours ago
    I can't possibly imagine what the parents are going through
    • vintagedave3 hours ago
      I found the description of how they moved apartment, but kept the old one with her room, very saddening. I get it - an aversion or a shrine, hard to say, or both I suspect (in grief I have had both feelings at the same time), but I get it.
  • shunhe4 hours ago
    This shows how important disclosures are. A field like this cannot learn if unsuccessful human experiments disappear while the corresponding animal work is published as promising.
  • 5 hours ago
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  • arjie4 hours ago
    What? The monkeys all had problems! Why do this? Just do PGT for your other kids. Come on, dude! Non lethal condition. Deranged behaviour.

    We did IVF with PGT and these days they tell you about carrier screening super early and everything here in California. I wouldn’t experiment on a real-life living human like this.

    A last ditch effort to save a life perhaps but come on, dude.

    If you're interested in the actual process of PGT and IVF, I wrote it down here: https://wiki.roshangeorge.dev/w/IVF

    Well-trodden ground and quite safe.

  • RS-2323 hours ago
    Surely this was preventable? I am surprised that immunologists and immunosuppressants weren’t part of the protocol here. Injecting trillions of viruses into spinal fluid sounds like a recipe for triggering a cytokine storm.

    It’s a tragic outcome, but her death is not in vain. The results need to be published for the public benefit, advancement in this area of research, and preventing similar outcomes.

  • tliltocatl5 hours ago
    TL;DR:

    - The girl had a really rare genetic disorder, traceable to a single-base mutation, that result in intellectual disability. Her case was quite mild, she was verbal and only had a learning disability, other cases are often far more severe.

    - They went for using adeno-associated virus as vector to deliver a CRISPR payload. It caused kidney and liver damage (AFAIUK due to immune response, not the virus itself? So hard to predict from an animal model.) which turned out fatal.

    - The family paid a significant share of the research funding and some off-record financial favors to the research team.

    - The research team's recent publication in Nature didn't mention the case at all (they basically chose keep silent about failures).

    The whole story has quite some Flowers for Algernon vibes except real life is way more cynical and sad. And I disliked the book back when I read it because it felt like a weepie just for the sake of weeping.

  • blondie9x3 hours ago
    Does anyone know what was the actual illness the girl had? I see a T was supposed to be a C but what is that? What are the long term implications?
  • raver19753 hours ago
    I hope they get their money back
  • morkalork4 hours ago
    Eugenics wars when?
  • trhway4 hours ago
    "Seven days after the girl’s medical team infused trillions of viruses carrying the recipe for the base editor into her spinal fluid, she died of a severe immune reaction linked to the therapy"

    questions of a layman - couldn't they initially do a small infusion of the [may be even weakened version of that] viruses to check for the immune reaction? May be such infusion would really serve as a vaccine prepping the immune system for the main infusion later? - though immune system killing the viruses may be nullifying the treatment - then may be when doing such therapy the patient needs to be [somewhat] immunosuppressed similar to transplant situations?

    • slashdave4 hours ago
      It could negate the treatment (the vector will be neutralized by the immune system).
      • trhway4 hours ago
        that is why after thinking a bit i edited the post adding the opposite track of thought - immunosuppression.
    • 395trek4 hours ago
      that's why in clinical trials you first do phase 1 human subjects where they are healthy and take small sub-therapeutic doses to test safety/tolerability. once it's established safe in humans they do phase 2 where they test if it works on sick people. Yeah I know this is different with transduction but they could at least test the vector first, maybe they did? Maybe some kind of lentivirus vector
    • HedonicEscal8r3 hours ago
      > May be such infusion would really serve as a vaccine prepping the immune system for the main infusion later?

      This is correct and exactly the problem. You don't want the immune system to react to the virus, but giving it exposure to the virus will nearly guarantee a reaction. This is why they were checking that the patient didn't have antibodies already.

      Here is an article discussing this issue: https://pmc.ncbi.nlm.nih.gov/articles/PMC10673641/

    • fwip4 hours ago
      The article mentions that she was given an immunosuppressant (prednisone), but that a more comprehensive course of immunouppressants could have been given.
    • elzbardico4 hours ago
      Acquired immunity is complicated territory. Doing this way could make a future adverse reaction more certain.

      But I don't think you're far from the correct procedure. Clinical trials are structured in phases. And AFAIK, safety is the first thing to be determined.

  • aa55b9c43e473645 hours ago
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  • Simulacra3 hours ago
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  • moralestapia4 hours ago
    "The young girl tugged on her mother’s hand as they pressed through the doors ..."

    Zack-D films tier writing there, disgusting.

  • Scroll_Swe4 hours ago
    This is the China future people on here want
  • nubg5 hours ago
    > The young girl tugged on her mother’s hand as they pressed through the doors of the hospital in Shanghai. She was 6 years old, bouncing along in a pink jacket and blue pants decorated with cartoon bears. Behind them, her father rolled a large suitcase with everything the child needed for the weeklong stay: stuffed animals, Play-Doh, an iPad loaded with episodes of Peppa Pig.

    What's this style of "journalism" (time-wasting) called and how can we exterminate it?

    • dghlsakjg5 hours ago
      It’s called long form feature writing. Many, many people enjoy it and do not want it exterminated. It’s a way to humanize and add emotion to complex topics. If you want, many outlets have bland straightforward bullet point articles. Try Axios.

      Reading articles posted on HN is optional as are most things on the internet. If you don’t like the style in the first paragraph, stop reading. Getting fewer eyeballs on an article is typically a way to “exterminate” a style. Be aware, the articles that make the biggest waves tend to be long form feature writing. Given their influence and popularity you might find your extermination efforts to be quixotic.

    • arjie3 hours ago
      It's human-interest style writing. Western, particularly North American, audiences strongly prefer this kind of scene-setting prose prior to information exchange. I am also not particularly a fan of it. In the past, you had to endure it. Nowadays, you can select for your own degree of expertise and terseness by feeding the prose into an LLM and prompting it appropriately. Therefore, complaints of this sort of writer-audience mismatch are no longer of use. Use the tools available to you to solve your problems.

      I used Opus 4.8 to avoid Fable guardrail hair-trigger, but you can use ChatGPT as well.

    • raincole5 hours ago
      Treat those proses as warnings. They mean the writers have decided to guide your emotions in certain direction instead of portraying what happened in a neutral tone.
      • orangedog4 hours ago
        They're writing about a child that died, I don't think they hav any other motive other than the reader to feel sadness or outrage and given it is a dead child, they should not.
        • 4 hours ago
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      • vintagedave3 hours ago
        I’ve written articles in this style. The goal is to be evocative of the story. Simple factual accounts carry less weight than the reader being present in the situation. To remain truthful and accurate you describe factually; it is not counter to that to also describe in a way that situates, evokes, humanizes something that is about the experience.

        This is about two uncertain, trusting parents taking their young daughter for treatment. It is in every way one of the most frightening human experiences. In that light, this is a light, gentle touch by the author trying to communicate to you the reader the humanity behind the facts.

      • hyperpape4 hours ago
        Did you describe what happened in a neutral tone?
      • GaryBluto4 hours ago
        Indeed. Whilst not the same situation, one of the things I realized while developing a filtering system for various websites was to be thankful for obnoxious mannerisms and phrases. You want people to keep using filtered phrases and such because said users are usually not worth the time anyway, even if they stopped using them.
    • trollbridge5 hours ago
      This is good quality journalism; human-interest details like this are important.
    • wrafawfwg5 hours ago
      All your comments boil down to: Why are people people and not machines?
    • garrybelka5 hours ago
      Velcro, I guess.
    • krick4 hours ago
      Yeah, this is insufferable. The title was interesting enough to click, but I don't know what to make of the audience that actually perceives this as a good source of information.
    • catlover765 hours ago
      This kind of thing is pretty standard, and you accordingly come across as rather boorish.

      But it is generally referred to as "creative non-fiction", and I agree it can often be overdone.

  • Hansenq4 hours ago
    This is a tragic story. But it is also a story about the lengths that parents in China will go to improve the quality of life for their only child or to "save face" to their social circle about how their child is performing relative to others.

    It's quite tragic that they felt the need to lean into this treatment and quite tragic that they were led on. Just a sad story all around.

    • laughing_man3 hours ago
      China officially ended its one-child policy in 2015. Barring medical reasons, there was no reason for their daughter to be their only child.
  • singpolyma35 hours ago
    Headline is the whole story. Sometimes a therapy doesn't work. Especially a new one
    • ncallaway5 hours ago
      > Headline is the whole story.

      That's just not true.

      From the article:

      > According to official documents and accounts provided by the girl’s parents, the hospital had allowed Qiu’s experimental treatment to proceed under a regulatory provision that does not require approval from national regulators. After the child’s death, the hospital paid a modest fine to a local health authority but Qiu was not publicly sanctioned.

      That's not in the headline, but is an important part of the story. Also from the article:

      > Seven experts in fields including genetics, virology, and bioethics who reviewed details of the Nature study and the clinical trial for Science and Retraction Watch expressed concern that Qiu and his team downplayed the trial’s risks in describing them to the parents, overlooked safety signals in animal studies, and proceeded even though success was unlikely.

      Also not in the headline, but also an important part of the story. Finally:

      > The girl’s parents, who requested that Science use pseudonyms for them and their daughter for privacy reasons, have decided to tell her story now because they are angry about what they feel is a lack of accountability by the researchers and the institutions. “Learning the reality of these missing safeguards has fundamentally changed how we now view the entire project,” says the father, a software engineer. He asked that he be called Jason, his wife Linda, and their daughter Mei (Chinese for “beautiful”). “We did not realize how unusual and dangerous many of the arrangements were.”

      Also not in the headline, also an important part of the story.

      • cogman105 hours ago
        Not to mention the part where it appears that the entire department decided to try and scam these parents.

        > Jeremy Sugarman, a medical doctor and bioethicist at Johns Hopkins University, says it’s not unusual for a family to bear the costs of developing a personalized treatment. But, according to text messages shared by Jason and Linda, Qiu also asked the couple to pay other members of the research team directly, through informal arrangements they found increasingly troubling.

        Qiu kept on adding on new back channel payments and seemed to keep ballooning the costs. I have to wonder if the procedure started because it was ready or because the parents ran out of resources.

        • neonstatic5 hours ago
          The part about gifts he received from the father in person is particularly vile.
          • rainprincess4 hours ago
            I think it's a part of the culture of guanxi (relations) in China.
      • dmix5 hours ago
        So it was a regulatory escape hatch for highly experimental medicine and it didn't work out?

        > The girl would be the first person in the world to receive a gene-editing therapy directed at the brain.

        The first person to ever try something comes with risks...

        • ncallaway5 hours ago
          And were those risks adequately communicated to the people taking them? According to the story, they weren't.

          That's a Big Fucking Deal, and is absolutely a significant part of the story.

          Was that in the headline?

          • dmix4 hours ago
            This is pretty silly. If you're paying $860k for something (note this is USD being spent within China), you can afford to do basic research on what you're getting involved with, which they apparently did:

            > The parents had heard about serious side effects, including deaths, caused by other gene therapies, and knew the greatest risk would be Mei’s immune response to the massive dose of virus.

            The risk was explicitly stated in the consent form:

            > The platelets in her blood also dropped to dangerous levels. It was the exact sequence of symptoms that the consent form had warned the family about.

            Qiu should have been more cautious in some of their communication with the obviously emotional parents, but this is pretty far from a scam and these aren't nobody doctors within China. He had a postdoc from UC San Diego, was a well known neuroscientist in China, published in Nature, etc.

            • shunhe4 hours ago
              There is a meaningful difference between knowing that gene therapy can cause serious complications in general and being told that every treated monkey developed moderate to severe liver damage, with one also showing kidney damage consistent with the mechanism that ultimately killed the child. Informed consent was pretty hard to get here
            • 0dayzan hour ago
              The team ignored the rests from the monkeys, and you're just shrugging it off?
    • fabian2k5 hours ago
      It's worse than that. The therapy likely killed her, and her condition wasn't fatal in the first place.
      • asqueella5 hours ago
        I was curious what non-fatal condition would make the parents so desperate (to participate in a first-in-human trial):

        > Mei was diagnosed with global developmental delay .. some of Mei’s behaviors .. were associated with autism.

        > CHD3 mutations produce a condition called Snijders Blok-Campeau syndrome

        > people with the mutation often have a normal life expectancy, but their symptoms vary widely. Most have slightly larger than normal heads, and about two-thirds have intellectual deficits. Moderate to severe cases may be nonverbal, suffer from seizures and heart problems, and have fluid-filled voids in their heads.

      • processing5 hours ago
        "global developmental delay" yeah this is tragic - this kid didn't need to go through this.
    • 5 hours ago
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