14 ms·

Teenager's sickle cell reversed using a treatment to change his DNA

211 points by _nh_ 10y ago

criddell 10y ago
Will this change potentially be transmitted to his children?
- maxerickson 10y ago
  It's unlikely. The virus used to modify the bone marrow cells would have to stay active after the transplant and infect the rest of his body (specifically his testicles).
  - helloworld 10y ago
    It sounds like this research involves somatic gene transfer, in which the change to the genome is not passed on to children: Gene transfer can be targeted to somatic (body) or germ (egg and sperm) cells. In somatic gene transfer the recipient's genome is changed, but the change is not passed on to the next generation. In germline gene transfer, the parents' egg and sperm cells are changed with the goal of passing on the changes to their offspring. https://www.genome.gov/10004764/germline-gene-transfer/ https://www.genome.gov/10004764/germline-gene-transfer/
    - candiodari 10y ago
      Isn't that dangerous ? This will allow him to have a normal life, which includes kids, which will need this (potentially very expensive) treatment as well. Wouldn't you, in order to not destroy the gene pool, want to restrict gene changes to both of those ? Either that or sterilize the patient to prevent transmission of lethal genes ? This treatment is VERY unfair to any children this guy fathers. Of course I do get that the method used here goes not really support germ transfer (that requires the gene change to happen in vitro)
      - JshWright 10y ago
        This is just a better treatment for sickle cell. Should sterilization be a requirement for any sickle cell treatment?
      - PhantomGremlin 10y ago
        This treatment is VERY unfair to any children this guy fathers. In order to have the disease you need to inherit bad genes from both parents.[1] Consequently there are many more carriers than people who actually have the trait. So any of this guy's children have at most a 50% chance of having the trait if the other parent of the child doesn't have it, and 0% chance if the other parent isn't a carrier. I'm sure if we sequenced your DNA we would find a number of potentially very problematic diseases for which you are a carrier. That applies to everyone, nobody has perfect DNA. in order to not destroy the gene pool There are a lot of morons in this world; many more being born every day. Many of them manage to reproduce before reaching the point where they would be under consideration for a Darwin Award. In the greater scheme of things this one particular genetic defect isn't seriously threatening to "destroy the gene pool". [1] https://en.wikipedia.org/wiki/Sickle-cell_disease https://en.wikipedia.org/wiki/Sickle-cell_disease
      - jfarlow 10y ago
        Part of the beauty of these kinds of gene therapies is that the cost can ultimately be lowered to near-zero levels. These are not drugs that must be taken over a lifetime, but can potentially provide 1-time delivery of the instructions to your own body about how to cure itself. Certainly in the near term the R&D must be paid for (and the marketing, and regulatory burden, and everything else). But in the long term the actual material used to change someone's life forever can cost pennies and a one-time delivery.
      - vidarh 10y ago
        Just carrying the sickle-cell trait is mostly neutral to highly advantageous depending on where you live, because it confers substantially increased resistance to Malaria. This is how a trait that is so dangerous when expressed has managed to spread; in regions with endemic malaria, carriers have better survival chances and the difference is sufficient to make up for those who express it and end up dying young. It is recessive - you need to inherit it from both parents to express it. So it is in fact entirely safe for this man to have children provided he has children with someone who is not a carrier, or ensure appropriate tests are taken during pregnancy. Most people who carry this trait in developed countries today know about it, because the mechanism is very clear and they will usually know whether or not any of their family expressed the trait, and will have been tested to see if they inherited it. E.g. we had our son tested because his mother is a carrier, but because I am not we knew he could not have sickle cell disease. My son is a carrier, but all that means is that like the guy in this article, he will want to make sure his partner is tested before having children, and to ensure to decide in advance what to do if both are carriers or if his partner has the disease (such as whether to have an abortion if tests show the child has the disease). We can expect the number of people with this gene to drop over time because it is now so easy to avoid. But in the meantime a treatment would make a massive difference for those with the disease.
  - apathy 10y ago
    This. It would need to affect F2. It won't.
  - apathy 10y ago
    This. It would need to affect F2. It won't.
- quotemstr 10y ago
  Unfortunately, human germline modification is still taboo here: https://motherboard.vice.com/en_us/article/scientists-argue-the-us-ban-on-human-gene-editing-will-leave-it-behind https://motherboard.vice.com/en_us/article/scientists-argue-... It angers me that a misguided and stringent sense of ethics might slow the deployment of one of the most beneficial technologies ever conceived.
  - Moshe_Silnorin 10y ago
    I agree with this, but not a popular opinion. Hence the down votes you are getting. Korea and China don't have the same memetic immune response to such ideas, injecting one's children with growth hormone in hope of increasing future job prospects, for example, is extremely common in Korea. I suspect embryo selection and generic engineering for increased IQ will take off in East Asia first. Then we will be forced to allow it to compete. 50+ more IQ points looks very possible: https://arxiv.org/abs/1408.3421 https://arxiv.org/abs/1408.3421 However, any significant lag could spell the end of American economic dominance. For this reason, I intend to start investing more in Korean firms in the next few decades.
    - deepnotderp 10y ago
      A better way to increase iq would be to raise the socioeconomic level...
      - cm2012 10y ago
        If genetic boosting is actually possible and not fringe bullshit, it's way faster than socioeconomic fixes, which seem to take 10 years per 3 iq points.
      - Moshe_Silnorin 10y ago
        Nope. Genetic engineering works far, far better. We've already plucked the low hanging fruit of adequate nutrition, early education, salt iodization, and lead reduction. Anyway, those reduce mental retardation, they don't improve the baseline too much. And the Flynn effect looks to be slowing or reversing. 50 IQ points is huge. It's the difference between a burger flipper and a physics professor. The change to the world when the average 5th grader is mastering chromodynamics is hard to even contemplate.
danielmorozoff 10y ago
here is the nejm paper in the article: http://www.nejm.org/doi/10.1056/NEJMoa1609677 http://www.nejm.org/doi/10.1056/NEJMoa1609677
- jfarlow 10y ago
  Ultimately, they are delivering a payload with a slightly modified version of wild-type hemoglobin (a single point mutation from wild-type). Patients with sickle-cell disease have a (different) mutation in their hemoglobin that causes the hemoglobin protein to aggregate, and not carry oxygen. The modified version being delivered to patients is not just a 'corrected, wild-type' version of the protein capable of carrying oxygen more efficiently, but actually carries a synthetic mutation that actually prevents the patient's version from aggregating. So if even 20% of the hemoglobin in the treated patient's blood is of this modified type, then none of their hemoglobin will aggregate, and they should get much of their oxygen-carrying capacity back. This modification to the introduced version of the protein also allows it to be easily identified and tracked to monitor things like its concentration. The actual sequence and mutation HBB [T87Q] protein: https://serotiny.bio/pinecone/part/10803 https://serotiny.bio/pinecone/part/10803 A short little writeup I did about the mutation: https://serotiny.bio/notes/proteins/hbb/ https://serotiny.bio/notes/proteins/hbb/ A very detailed presentation about Bluebird Bio's therapy (called LentiGlobin BB305) provided to the government: (PDF warning) http://osp.od.nih.gov/sites/default/files/1164_bluebirdbio.pdf http://osp.od.nih.gov/sites/default/files/1164_bluebirdbio.p...
M_Grey 10y ago
What an amazing achievement. Finally, the promise of genetic therapy is starting to actually emerge from the lab.
aptidude187 10y ago
Total noob here, is this type of treatment going in the direction of something like in the movie gattaca? Would gene editing also help fully grown adults?
- apathy 10y ago
  If they have an identifiable deficiency, sure. Sickle cell is a stem cell (erythroblast more precisely) disorder, so fixing the stem cells fixes the disease. If you already have the tissues you want to change, it'll be harder.
- red75prime 10y ago
  Real life gattaca would be quite boring. Protagonist would have failed practical aptitude tests or some such.
  - true_religion 10y ago
    He cheated. He had a heart condition but faked his heart rate for the testing so he would be allowed to go into space. Yes, he could run at the same pace as someone with a better heart, but he was predisposed to arrhythmias even at a normal level of effort.
jasonkolb 10y ago
Is this using CRISPR or some other method of editing the DNA?
- jfarlow 10y ago
  This treatment does not use CRISPR. It involves the hollowed out and repurposed lentivirus (similar in kind to HIV)[1]. The virus keeps it's own viral 'insert-into-DNA' machinery, but is stripped of its replication machinery as well as the code for its physical shell. The insert-into-DNA machinery is further hijacked so it can insert nothing but the DNA that encodes for the new mutated hemoglobin (HBB [T87Q][2]) that, when the patient's cell reads that new DNA will produce a new version of the protein. That insertion machinery with its new payload is loaded into a viral shell in a lab somewhere (again, its replication machinery and the code for new shells has been gutted). When this new virus is given to the patients it does indeed infect the patients' cells. It uses its viral machinery to insert itself into the genome of the patient, more or less randomly - and that is not ideal. CRISPR systems are much newer and are being worked on right now, but the technologies you see in use in this article predate CRISPR. CRISPR will only speed up what was here a monumental (and slightly more risky) effort. Regardless of how the code gets inserted into the genome (lentiviral in this case, CRISPR likely in future therapies), the instruction set to produce the new protein is not only capable of doing the job of the broken hemoglobin, but actually enables the broken hemoglobin to regain some of its function, likely coming very close to actually curing the patient. In computer terms, someone with sickle-cell disease has a typo in the source code that leads to a buffer overflow error in the oxygen transport module. We found stuxnet can inject live code into a running OS, so we stripped it of its payload, it's ability to replicate but kept its injection capabilities and gave it our hot-fix as its payload. Our patch will be injected into billions of running nodes, inserting a ~500 line patch randomly into the each node's memory stack (yes, that's scary - but if a few of the nodes (cells) go down, it's not a horrible problem, and the current price of doing the patch at all... CRISPR can help here in future versions). That new code provides not only an alternative oxygen transport package, but this new package, so long as its running on >20% of the nodes, actually forces the original code's memory to periodically flush, thus de facto correcting the original typo's overflow bug - allowing both the new package and the old (kinda bug-fixed) package to both now be useful oxygen transport code. No more bug = cure. The patients had a code regression, and we're applying not just a 1.0 fix, but a very real 1.1 patch on the human hemoglobin instruction set (randomly, into live code, on millions if not billions of cells, using modified HIV technology). Diagram of the patch's entire injected instruction set (8.5kb): https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=4779296_fig-3.jpg https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/t... [1] Lentivirus: https://en.wikipedia.org/wiki/Lentivirus https://en.wikipedia.org/wiki/Lentivirus [2] The 'updated' hemoglobin: https://serotiny.bio/notes/proteins/hbb/ https://serotiny.bio/notes/proteins/hbb/
beerbaron23 10y ago
Would this apply to thalassemia too?
hutzlibu 10y ago
"He no longer requires a transfusion so we are quite pleased with that" I like that language so much more than, than the increasing THIS IS AMAZING, SO AWESOME, WHAT WE GREAT GUYS ACCOMPLISHED!!! even though it would fit here much more, than in the usual context people use it fore ...
- Waterluvian 10y ago
  I don't think I have ever seen medical professionals speak in the manner you described.
  - hutzlibu 10y ago
    I did not say that, I was talking about other tech branches, startup hype speak etc.
    - Waterluvian 10y ago
      Aha my mistake.
Symmetry 10y ago
After adenoviruses proved to be dangerous [1] I wonder what sort of virus they're using now? [1] https://en.wikipedia.org/wiki/Jesse_Gelsinger https://en.wikipedia.org/wiki/Jesse_Gelsinger Are doctors allowed to use gene therapy in life or death conditions now? In the trial for fixing OTC deficiency that Jesse Gelsinger died in they only administered the trial to people who were capable of living with the disease as opposed to the babies that were going to die in their first year without it. The idea was that a parent faced with the possibility of their child dying painfully couldn't possibly refuse the treatment and therefore couldn't give informed consent.
- shagie 10y ago
  A key point in the difference that might help explain it: > On 13 September 1999, Gelsinger was injected with an adenoviral vector carrying a corrected gene to test the safety of the procedure vs. > Doctors removed his bone marrow - the part of the body that makes blood. They then genetically altered it in a lab to compensate for the defect in his DNA that caused the disease. ... > A virus was used to infect the bone marrow with new, correct instructions. > The corrected bone marrow was then put back into the patient. This was a self transfusion in the lab rather than an injection of a virus. After the virus infected the bone marrow, it would then have been tested to make sure that there are no immune responses with the material and that it is safe to return to the patient.
- ralfd 10y ago
  > The idea was that a parent faced with the possibility of their child dying painfully couldn't possibly refuse the treatment and therefore couldn't give informed consent. Well ... I get the idea, but I am not sure this is rational. If I have the choice between pizza and no pizza, and of course everyone would choose the pizza, my choice is not uninformed, just because it is too good of a deal.
  - true_religion 10y ago
    The idea is that they would agree to anything, including things which has low likelihood of success and could be traumatic to the child simply because the known downside was too great. People aren't very good at comparing a terrible known condition A, to a merely potentially terrible known condition B.

211 points by _nh_ 10y ago

criddell 10y ago

Will this change potentially be transmitted to his children?

maxerickson 10y ago
It's unlikely. The virus used to modify the bone marrow cells would have to stay active after the transplant and infect the rest of his body (specifically his testicles).
- helloworld 10y ago
  It sounds like this research involves somatic gene transfer, in which the change to the genome is not passed on to children: Gene transfer can be targeted to somatic (body) or germ (egg and sperm) cells. In somatic gene transfer the recipient's genome is changed, but the change is not passed on to the next generation. In germline gene transfer, the parents' egg and sperm cells are changed with the goal of passing on the changes to their offspring. https://www.genome.gov/10004764/germline-gene-transfer/ https://www.genome.gov/10004764/germline-gene-transfer/
  - candiodari 10y ago
    Isn't that dangerous ? This will allow him to have a normal life, which includes kids, which will need this (potentially very expensive) treatment as well. Wouldn't you, in order to not destroy the gene pool, want to restrict gene changes to both of those ? Either that or sterilize the patient to prevent transmission of lethal genes ? This treatment is VERY unfair to any children this guy fathers. Of course I do get that the method used here goes not really support germ transfer (that requires the gene change to happen in vitro)
    - JshWright 10y ago
      This is just a better treatment for sickle cell. Should sterilization be a requirement for any sickle cell treatment?
    - PhantomGremlin 10y ago
      This treatment is VERY unfair to any children this guy fathers. In order to have the disease you need to inherit bad genes from both parents.[1] Consequently there are many more carriers than people who actually have the trait. So any of this guy's children have at most a 50% chance of having the trait if the other parent of the child doesn't have it, and 0% chance if the other parent isn't a carrier. I'm sure if we sequenced your DNA we would find a number of potentially very problematic diseases for which you are a carrier. That applies to everyone, nobody has perfect DNA. in order to not destroy the gene pool There are a lot of morons in this world; many more being born every day. Many of them manage to reproduce before reaching the point where they would be under consideration for a Darwin Award. In the greater scheme of things this one particular genetic defect isn't seriously threatening to "destroy the gene pool". [1] https://en.wikipedia.org/wiki/Sickle-cell_disease https://en.wikipedia.org/wiki/Sickle-cell_disease
    - jfarlow 10y ago
      Part of the beauty of these kinds of gene therapies is that the cost can ultimately be lowered to near-zero levels. These are not drugs that must be taken over a lifetime, but can potentially provide 1-time delivery of the instructions to your own body about how to cure itself. Certainly in the near term the R&D must be paid for (and the marketing, and regulatory burden, and everything else). But in the long term the actual material used to change someone's life forever can cost pennies and a one-time delivery.
    - vidarh 10y ago
      Just carrying the sickle-cell trait is mostly neutral to highly advantageous depending on where you live, because it confers substantially increased resistance to Malaria. This is how a trait that is so dangerous when expressed has managed to spread; in regions with endemic malaria, carriers have better survival chances and the difference is sufficient to make up for those who express it and end up dying young. It is recessive - you need to inherit it from both parents to express it. So it is in fact entirely safe for this man to have children provided he has children with someone who is not a carrier, or ensure appropriate tests are taken during pregnancy. Most people who carry this trait in developed countries today know about it, because the mechanism is very clear and they will usually know whether or not any of their family expressed the trait, and will have been tested to see if they inherited it. E.g. we had our son tested because his mother is a carrier, but because I am not we knew he could not have sickle cell disease. My son is a carrier, but all that means is that like the guy in this article, he will want to make sure his partner is tested before having children, and to ensure to decide in advance what to do if both are carriers or if his partner has the disease (such as whether to have an abortion if tests show the child has the disease). We can expect the number of people with this gene to drop over time because it is now so easy to avoid. But in the meantime a treatment would make a massive difference for those with the disease.
- apathy 10y ago
  This. It would need to affect F2. It won't.
- apathy 10y ago
  This. It would need to affect F2. It won't.
quotemstr 10y ago
Unfortunately, human germline modification is still taboo here: https://motherboard.vice.com/en_us/article/scientists-argue-the-us-ban-on-human-gene-editing-will-leave-it-behind https://motherboard.vice.com/en_us/article/scientists-argue-... It angers me that a misguided and stringent sense of ethics might slow the deployment of one of the most beneficial technologies ever conceived.
- Moshe_Silnorin 10y ago
  I agree with this, but not a popular opinion. Hence the down votes you are getting. Korea and China don't have the same memetic immune response to such ideas, injecting one's children with growth hormone in hope of increasing future job prospects, for example, is extremely common in Korea. I suspect embryo selection and generic engineering for increased IQ will take off in East Asia first. Then we will be forced to allow it to compete. 50+ more IQ points looks very possible: https://arxiv.org/abs/1408.3421 https://arxiv.org/abs/1408.3421 However, any significant lag could spell the end of American economic dominance. For this reason, I intend to start investing more in Korean firms in the next few decades.
  - deepnotderp 10y ago
    A better way to increase iq would be to raise the socioeconomic level...
    - cm2012 10y ago
      If genetic boosting is actually possible and not fringe bullshit, it's way faster than socioeconomic fixes, which seem to take 10 years per 3 iq points.
    - Moshe_Silnorin 10y ago
      Nope. Genetic engineering works far, far better. We've already plucked the low hanging fruit of adequate nutrition, early education, salt iodization, and lead reduction. Anyway, those reduce mental retardation, they don't improve the baseline too much. And the Flynn effect looks to be slowing or reversing. 50 IQ points is huge. It's the difference between a burger flipper and a physics professor. The change to the world when the average 5th grader is mastering chromodynamics is hard to even contemplate.

danielmorozoff 10y ago

here is the nejm paper in the article: http://www.nejm.org/doi/10.1056/NEJMoa1609677 http://www.nejm.org/doi/10.1056/NEJMoa1609677

jfarlow 10y ago
Ultimately, they are delivering a payload with a slightly modified version of wild-type hemoglobin (a single point mutation from wild-type). Patients with sickle-cell disease have a (different) mutation in their hemoglobin that causes the hemoglobin protein to aggregate, and not carry oxygen. The modified version being delivered to patients is not just a 'corrected, wild-type' version of the protein capable of carrying oxygen more efficiently, but actually carries a synthetic mutation that actually prevents the patient's version from aggregating. So if even 20% of the hemoglobin in the treated patient's blood is of this modified type, then none of their hemoglobin will aggregate, and they should get much of their oxygen-carrying capacity back. This modification to the introduced version of the protein also allows it to be easily identified and tracked to monitor things like its concentration. The actual sequence and mutation HBB [T87Q] protein: https://serotiny.bio/pinecone/part/10803 https://serotiny.bio/pinecone/part/10803 A short little writeup I did about the mutation: https://serotiny.bio/notes/proteins/hbb/ https://serotiny.bio/notes/proteins/hbb/ A very detailed presentation about Bluebird Bio's therapy (called LentiGlobin BB305) provided to the government: (PDF warning) http://osp.od.nih.gov/sites/default/files/1164_bluebirdbio.pdf http://osp.od.nih.gov/sites/default/files/1164_bluebirdbio.p...

M_Grey 10y ago

What an amazing achievement. Finally, the promise of genetic therapy is starting to actually emerge from the lab.

aptidude187 10y ago

Total noob here, is this type of treatment going in the direction of something like in the movie gattaca? Would gene editing also help fully grown adults?

apathy 10y ago
If they have an identifiable deficiency, sure. Sickle cell is a stem cell (erythroblast more precisely) disorder, so fixing the stem cells fixes the disease. If you already have the tissues you want to change, it'll be harder.
red75prime 10y ago
Real life gattaca would be quite boring. Protagonist would have failed practical aptitude tests or some such.
- true_religion 10y ago
  He cheated. He had a heart condition but faked his heart rate for the testing so he would be allowed to go into space. Yes, he could run at the same pace as someone with a better heart, but he was predisposed to arrhythmias even at a normal level of effort.

jasonkolb 10y ago

Is this using CRISPR or some other method of editing the DNA?

jfarlow 10y ago
This treatment does not use CRISPR. It involves the hollowed out and repurposed lentivirus (similar in kind to HIV)[1]. The virus keeps it's own viral 'insert-into-DNA' machinery, but is stripped of its replication machinery as well as the code for its physical shell. The insert-into-DNA machinery is further hijacked so it can insert nothing but the DNA that encodes for the new mutated hemoglobin (HBB [T87Q][2]) that, when the patient's cell reads that new DNA will produce a new version of the protein. That insertion machinery with its new payload is loaded into a viral shell in a lab somewhere (again, its replication machinery and the code for new shells has been gutted). When this new virus is given to the patients it does indeed infect the patients' cells. It uses its viral machinery to insert itself into the genome of the patient, more or less randomly - and that is not ideal. CRISPR systems are much newer and are being worked on right now, but the technologies you see in use in this article predate CRISPR. CRISPR will only speed up what was here a monumental (and slightly more risky) effort. Regardless of how the code gets inserted into the genome (lentiviral in this case, CRISPR likely in future therapies), the instruction set to produce the new protein is not only capable of doing the job of the broken hemoglobin, but actually enables the broken hemoglobin to regain some of its function, likely coming very close to actually curing the patient. In computer terms, someone with sickle-cell disease has a typo in the source code that leads to a buffer overflow error in the oxygen transport module. We found stuxnet can inject live code into a running OS, so we stripped it of its payload, it's ability to replicate but kept its injection capabilities and gave it our hot-fix as its payload. Our patch will be injected into billions of running nodes, inserting a ~500 line patch randomly into the each node's memory stack (yes, that's scary - but if a few of the nodes (cells) go down, it's not a horrible problem, and the current price of doing the patch at all... CRISPR can help here in future versions). That new code provides not only an alternative oxygen transport package, but this new package, so long as its running on >20% of the nodes, actually forces the original code's memory to periodically flush, thus de facto correcting the original typo's overflow bug - allowing both the new package and the old (kinda bug-fixed) package to both now be useful oxygen transport code. No more bug = cure. The patients had a code regression, and we're applying not just a 1.0 fix, but a very real 1.1 patch on the human hemoglobin instruction set (randomly, into live code, on millions if not billions of cells, using modified HIV technology). Diagram of the patch's entire injected instruction set (8.5kb): https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=4779296_fig-3.jpg https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/t... [1] Lentivirus: https://en.wikipedia.org/wiki/Lentivirus https://en.wikipedia.org/wiki/Lentivirus [2] The 'updated' hemoglobin: https://serotiny.bio/notes/proteins/hbb/ https://serotiny.bio/notes/proteins/hbb/

beerbaron23 10y ago

Would this apply to thalassemia too?

hutzlibu 10y ago

"He no longer requires a transfusion so we are quite pleased with that" I like that language so much more than, than the increasing THIS IS AMAZING, SO AWESOME, WHAT WE GREAT GUYS ACCOMPLISHED!!! even though it would fit here much more, than in the usual context people use it fore ...

Waterluvian 10y ago
I don't think I have ever seen medical professionals speak in the manner you described.
- hutzlibu 10y ago
  I did not say that, I was talking about other tech branches, startup hype speak etc.
  - Waterluvian 10y ago
    Aha my mistake.

Symmetry 10y ago

After adenoviruses proved to be dangerous [1] I wonder what sort of virus they're using now? [1] https://en.wikipedia.org/wiki/Jesse_Gelsinger https://en.wikipedia.org/wiki/Jesse_Gelsinger Are doctors allowed to use gene therapy in life or death conditions now? In the trial for fixing OTC deficiency that Jesse Gelsinger died in they only administered the trial to people who were capable of living with the disease as opposed to the babies that were going to die in their first year without it. The idea was that a parent faced with the possibility of their child dying painfully couldn't possibly refuse the treatment and therefore couldn't give informed consent.

shagie 10y ago
A key point in the difference that might help explain it: > On 13 September 1999, Gelsinger was injected with an adenoviral vector carrying a corrected gene to test the safety of the procedure vs. > Doctors removed his bone marrow - the part of the body that makes blood. They then genetically altered it in a lab to compensate for the defect in his DNA that caused the disease. ... > A virus was used to infect the bone marrow with new, correct instructions. > The corrected bone marrow was then put back into the patient. This was a self transfusion in the lab rather than an injection of a virus. After the virus infected the bone marrow, it would then have been tested to make sure that there are no immune responses with the material and that it is safe to return to the patient.
ralfd 10y ago
> The idea was that a parent faced with the possibility of their child dying painfully couldn't possibly refuse the treatment and therefore couldn't give informed consent. Well ... I get the idea, but I am not sure this is rational. If I have the choice between pizza and no pizza, and of course everyone would choose the pizza, my choice is not uninformed, just because it is too good of a deal.
- true_religion 10y ago
  The idea is that they would agree to anything, including things which has low likelihood of success and could be traumatic to the child simply because the known downside was too great. People aren't very good at comparing a terrible known condition A, to a merely potentially terrible known condition B.