10 ms·

In layman's terms: She had a particularly vicious form of cancer where the very cells that are supposed to protect your health -- your T-cells -- are the enemy.

In layman's terms: She had a particularly vicious form of cancer where the very cells that are supposed to protect your health -- your T-cells -- are the enemy. So they made three edits to donor cells and wiped out her compromised cells. Then gave her a bone marrow transplant afterwards to replenish her immune system with new cells. I'm squeamish about genetic research, but this looks really good to me. I hope she recovers fully and there are no further complications, though I imagine it's too early to guess what her prognosis might be. So there are already trials of base editing under way in sickle-cell disease, as well as high cholesterol that runs in families and the blood disorder beta-thalassemia. That's a big deal for people with those genetic disorders.

GenerocUsername 4y ago
I feel like this type of medicine is more like a research study waiting for a perfect match patient than it is highly personalized treatment... Is this technique broadly applicable? Or limited to very specific cases
- DoreenMichele 4y ago
  It looks to me like a somewhat unique opportunity to risk it because without this treatment, she was dead anyway and in fairly short order. So it was a means for them to learn something with very little potential downside. Worst case scenario: The treatment kills her. And she was dying anyway. From the article: In Alyssa's therapy, each of the base edits involved breaking a section of genetic code so it no longer worked. But there are more nuanced applications where instead of switching an instruction off you can fix a defective one. Sickle-cell anaemia, for example, is caused by just one base change that could be corrected. And I already quoted (in my previous comment) the next paragraph that indicates they are already doing trials. This is potentially a big deal and they seem to be pursuing it in a very reasonable and conservative fashion, which is always something that concerns me with this type thing. There's a lot of potential for terrible and horrifying abuse and that is not what I am seeing described here.
  - runnerup 4y ago
    Seems like this particular version of gene editing only works with blood/marrow disorders? If someone had a single mutation affecting their colon or eye, would the same technique be appropriate?
    - markus92 4y ago
      Blood/bone marrow is relatively easy as you have a very clear delivery vehicle for your modified genes. Actually getting to the colon cells or retina is a lot harder, can’t just inject it into the blood and expect it to end up in the right place.
  - pbronez 4y ago
    Yeah, those are valuable opportunities. You have to take risks to learn, but human life is to valuable to risk. I remember looking into the state of the art around in utero and neonatal health when we got pregnant. I was astonished at how limited the knowledge is. I quickly realized the big gaps are just because it’s too risky to study. You can’t morally experiment on pregnant people and infants.
- gizmo686 4y ago
  A "problem" with this treatment is that, for most patients, the current standard of care works. To the extent that this treatment is effective, it is likely effective for most leukaemia patients, including those who would respond well to current treatments. It is very plausible that this treatment (or a refined version of it) will eventually be shown to be superior to the current standard of care, in which case it would become the standard of care, and the current treatment will be relegated to the niche patient that does not respond to gene edited t-cells. More broadly, the technique of precisely editing DNA of select cells to perform specific engineered tasks is very broadly applicable. But that is a technique for developing treatments, not a treatment itself.
  - walkerbrown 4y ago
    > will eventually be shown to be superior to the current standard of care, in which case it would become the standard of care How does this overturning occur? Do care providers agitate for change? Or is it typically a response to headstrong patients and families?
    - Someone 4y ago
      It starts with researchers convincing their ethical review board that they should be given the opportunity to experiment with the different approach. That’s why new procedures almost always are done on patients who are as good as dead (gene editing to change one’s hair color won’t soon get past ethical review, for example, but if gene editing gets used in mainstream medicine, enough data may be collected to make a review board say it’s acceptable to give it a try) The first experiments typically only prove the medicine or procedure works. Long term survival of the patient the exception. From there, it’s step by step towards treating healthier and healthier patients. If it turns out the approach is better for the typical patient, patient groups (who may even have paid for part of the research) start lobbying for its use. If the new procedure is both better and cheaper, insurers also will lobby for it.
  - throwuwu 4y ago
    Isn’t this treatment simply accomplishing the same thing that the current treatment does but in a targeted way with hopefully much fewer side effects? When you have cancerous T cells the only option is to eradicate all of them and start over with a bone marrow transplant. Normally that would mean frying them with radiation or poisoning with chemo which also effects a lot of other tissue. This treatment is supposed to only kill the T cells.
- l33tman 4y ago
  Wiping out the recipients immune system and transplanting a donor system is in itself a common (advanced) practice since long, so the new part here is the tweaking of the donor system. Very interesting.
  - maxerickson 4y ago
    The edited cells did not replace her immune system. They were used to destroy it. Then after that a bone marrow transplant was done to restore it.
- christkv 4y ago
  Its coming within the decade for cancer vaccines. The trick is to be able to scale production and lower the turnaround time.
- phkahler 4y ago
  Wiping out your immune system and replacing it has something like a 50/50 survival rate even if you use your own cells. It's a hail Mary than usually either kills or cures. I knew a guy with cancer that had this done. He survived the process, but unfortunately the cells they restored him with were not cancer free like they thought. He died anyway. I think increasing the survival rate for these things could be very useful.
emmelaich 4y ago
Very interesting, because T-cells are implicated in multiple sclerosis. And probably other similar diseases.
- lostlogin 4y ago
  The detective work going on with MS is fascinating. The blood work from the US military and what it has shown is really interesting - it’s not new news but was to me when I stumbled on it this year. https://www.nih.gov/news-events/nih-research-matters/study-suggests-epstein-barr-virus-may-cause-multiple-sclerosis https://www.nih.gov/news-events/nih-research-matters/study-s...
  - lebuffon 4y ago
    I have long suspected that viruses are the underlying cause of most of the diseases that have eluded us for the last 50 years. HIV gave us insights into a novel way that viruses can operate. It makes sense to think that there are more ways than we imagined. E/B virus is suspect in Type 1 Diabetes too. E/B Vaccination could eradicate a group of diseases potentially.
inglor_cz 4y ago
Resetting the immune system can be already done and it seems to help against auto-immune diseases such as lupus, but it is very dangerous. Once you destroy the immune system of the patient, and before it grows back from donor cells, the patient is fatally vulnerable even to normally banal pathogens such as the common cold. Keeping the patient isolated and alive in a hospital full of germs is a major challenge. That is why this kind of therapy is only used when the patient faces death anyway.
mcculley 4y ago
> I'm squeamish about genetic research Can you elaborate on what makes you squeamish about research?
- yitianjian 4y ago
  Not OP, but something just feels unnatural and unsettling about changing humans, and especially for changing yourself. It feels like the uncanny valley where it just doesn't feel right. I'm agnostic so it's not for a particularly religious reasons, and it's purely an emotional response for me that's not grounded in logic at all, so I also just describe it as squeamish for no reason.
  - sinenomine 4y ago
    Thank you for a honest response. I think this is an underexplored topic - how many of our broad social policies were shaped mostly on the basis of sufficiently broadly shared visceral feeling. Should we base ultimately coercive society-wide regulatory framework on mere "squeamishness", appropriately rationalized, or should we instead embrace a non-discriminatory, laissez-faire approach in this domain?
    - quesera 4y ago
      > how many of our broad social policies were shaped mostly on the basis of sufficiently broadly shared visceral feeling All of them? I'm struggling to think of a counterexample.
      - vcxy 4y ago
        Yeah, I'd say the phrases "broadly shared visceral feelings" and "broad social policies" point to nearly the same concept.
  - BurningFrog 4y ago
    When I have these thoughts, I remind myself that typhoid is natural and penicillin is artificial. A big part of progress is fighting and defeating the natural. That said, not all genetic manipulation will end well.
sinenomine 4y ago
>I'm squeamish about genetic research And I'm sad about millions upon millions of mostly well-meaning people, who died of ultimately preventable causes - if only we could push the research from the lab to clinic faster. Everybody is prone to ageing, and very soon it will be our turn.
- lettergram 4y ago
  The challenge with genetics research is it could also result in the death of every human on the planet. It’s an amazing power for good and bad.
  - sinenomine 4y ago
    You don't need to ban, say, clinical trials of gene therapy (especially with inert lipid nanoparticle carriers which do not replicate), to ban a quite narrow and not really clinically useful subfield called "gain of function research". Why can't our legal system deter the obvious high-level publicly visible perpetrators of the recent "gain-of-function" fiasco is really some food for thought.
    - shadowgovt 4y ago
      As a general rule, we don't arrest people for things that aren't illegal. ... Unless by "deter" you just meant "make it illegal," in which case, agreed.
    - lettergram 4y ago
      It’s more than broad weaponization of viruses that are a danger though. Take for instance what we’re doing with plants. We make designer plants that provide food, and are immune from particular pesticides. We then spray the fields and all the other plants and bugs die (besides the immune plants). What happens when it turns out some genetic inserts in the corn creates something like mad cow disease (but in humans) 3-5 years later? Turns out some protein the corn produced we thought was harmless caused massive issues. Genetics has massive implications even if well meaning. I think the ability to eliminate disease is massively powerful and a net good. That said, I’m concerned about the long term tail end risks of such work. I don’t think you can ban it, because someone will do the work. And those that do the work will get a competitive advantage (eventually letting them “win”). I think it’s about mitigating risks by reducing / limiting mass adoption of genetic based technology without a very long window of analysis.

GenerocUsername 4y ago

I feel like this type of medicine is more like a research study waiting for a perfect match patient than it is highly personalized treatment... Is this technique broadly applicable? Or limited to very specific cases

DoreenMichele 4y ago
It looks to me like a somewhat unique opportunity to risk it because without this treatment, she was dead anyway and in fairly short order. So it was a means for them to learn something with very little potential downside. Worst case scenario: The treatment kills her. And she was dying anyway. From the article: In Alyssa's therapy, each of the base edits involved breaking a section of genetic code so it no longer worked. But there are more nuanced applications where instead of switching an instruction off you can fix a defective one. Sickle-cell anaemia, for example, is caused by just one base change that could be corrected. And I already quoted (in my previous comment) the next paragraph that indicates they are already doing trials. This is potentially a big deal and they seem to be pursuing it in a very reasonable and conservative fashion, which is always something that concerns me with this type thing. There's a lot of potential for terrible and horrifying abuse and that is not what I am seeing described here.
- runnerup 4y ago
  Seems like this particular version of gene editing only works with blood/marrow disorders? If someone had a single mutation affecting their colon or eye, would the same technique be appropriate?
  - markus92 4y ago
    Blood/bone marrow is relatively easy as you have a very clear delivery vehicle for your modified genes. Actually getting to the colon cells or retina is a lot harder, can’t just inject it into the blood and expect it to end up in the right place.
- pbronez 4y ago
  Yeah, those are valuable opportunities. You have to take risks to learn, but human life is to valuable to risk. I remember looking into the state of the art around in utero and neonatal health when we got pregnant. I was astonished at how limited the knowledge is. I quickly realized the big gaps are just because it’s too risky to study. You can’t morally experiment on pregnant people and infants.
gizmo686 4y ago
A "problem" with this treatment is that, for most patients, the current standard of care works. To the extent that this treatment is effective, it is likely effective for most leukaemia patients, including those who would respond well to current treatments. It is very plausible that this treatment (or a refined version of it) will eventually be shown to be superior to the current standard of care, in which case it would become the standard of care, and the current treatment will be relegated to the niche patient that does not respond to gene edited t-cells. More broadly, the technique of precisely editing DNA of select cells to perform specific engineered tasks is very broadly applicable. But that is a technique for developing treatments, not a treatment itself.
- walkerbrown 4y ago
  > will eventually be shown to be superior to the current standard of care, in which case it would become the standard of care How does this overturning occur? Do care providers agitate for change? Or is it typically a response to headstrong patients and families?
  - Someone 4y ago
    It starts with researchers convincing their ethical review board that they should be given the opportunity to experiment with the different approach. That’s why new procedures almost always are done on patients who are as good as dead (gene editing to change one’s hair color won’t soon get past ethical review, for example, but if gene editing gets used in mainstream medicine, enough data may be collected to make a review board say it’s acceptable to give it a try) The first experiments typically only prove the medicine or procedure works. Long term survival of the patient the exception. From there, it’s step by step towards treating healthier and healthier patients. If it turns out the approach is better for the typical patient, patient groups (who may even have paid for part of the research) start lobbying for its use. If the new procedure is both better and cheaper, insurers also will lobby for it.
- throwuwu 4y ago
  Isn’t this treatment simply accomplishing the same thing that the current treatment does but in a targeted way with hopefully much fewer side effects? When you have cancerous T cells the only option is to eradicate all of them and start over with a bone marrow transplant. Normally that would mean frying them with radiation or poisoning with chemo which also effects a lot of other tissue. This treatment is supposed to only kill the T cells.
l33tman 4y ago
Wiping out the recipients immune system and transplanting a donor system is in itself a common (advanced) practice since long, so the new part here is the tweaking of the donor system. Very interesting.
- maxerickson 4y ago
  The edited cells did not replace her immune system. They were used to destroy it. Then after that a bone marrow transplant was done to restore it.
christkv 4y ago
Its coming within the decade for cancer vaccines. The trick is to be able to scale production and lower the turnaround time.
phkahler 4y ago
Wiping out your immune system and replacing it has something like a 50/50 survival rate even if you use your own cells. It's a hail Mary than usually either kills or cures. I knew a guy with cancer that had this done. He survived the process, but unfortunately the cells they restored him with were not cancer free like they thought. He died anyway. I think increasing the survival rate for these things could be very useful.

emmelaich 4y ago

Very interesting, because T-cells are implicated in multiple sclerosis. And probably other similar diseases.

lostlogin 4y ago
The detective work going on with MS is fascinating. The blood work from the US military and what it has shown is really interesting - it’s not new news but was to me when I stumbled on it this year. https://www.nih.gov/news-events/nih-research-matters/study-suggests-epstein-barr-virus-may-cause-multiple-sclerosis https://www.nih.gov/news-events/nih-research-matters/study-s...
- lebuffon 4y ago
  I have long suspected that viruses are the underlying cause of most of the diseases that have eluded us for the last 50 years. HIV gave us insights into a novel way that viruses can operate. It makes sense to think that there are more ways than we imagined. E/B virus is suspect in Type 1 Diabetes too. E/B Vaccination could eradicate a group of diseases potentially.

inglor_cz 4y ago

Resetting the immune system can be already done and it seems to help against auto-immune diseases such as lupus, but it is very dangerous. Once you destroy the immune system of the patient, and before it grows back from donor cells, the patient is fatally vulnerable even to normally banal pathogens such as the common cold. Keeping the patient isolated and alive in a hospital full of germs is a major challenge. That is why this kind of therapy is only used when the patient faces death anyway.

mcculley 4y ago

> I'm squeamish about genetic research Can you elaborate on what makes you squeamish about research?

yitianjian 4y ago
Not OP, but something just feels unnatural and unsettling about changing humans, and especially for changing yourself. It feels like the uncanny valley where it just doesn't feel right. I'm agnostic so it's not for a particularly religious reasons, and it's purely an emotional response for me that's not grounded in logic at all, so I also just describe it as squeamish for no reason.
- sinenomine 4y ago
  Thank you for a honest response. I think this is an underexplored topic - how many of our broad social policies were shaped mostly on the basis of sufficiently broadly shared visceral feeling. Should we base ultimately coercive society-wide regulatory framework on mere "squeamishness", appropriately rationalized, or should we instead embrace a non-discriminatory, laissez-faire approach in this domain?
  - quesera 4y ago
    > how many of our broad social policies were shaped mostly on the basis of sufficiently broadly shared visceral feeling All of them? I'm struggling to think of a counterexample.
    - vcxy 4y ago
      Yeah, I'd say the phrases "broadly shared visceral feelings" and "broad social policies" point to nearly the same concept.
- BurningFrog 4y ago
  When I have these thoughts, I remind myself that typhoid is natural and penicillin is artificial. A big part of progress is fighting and defeating the natural. That said, not all genetic manipulation will end well.

sinenomine 4y ago

>I'm squeamish about genetic research And I'm sad about millions upon millions of mostly well-meaning people, who died of ultimately preventable causes - if only we could push the research from the lab to clinic faster. Everybody is prone to ageing, and very soon it will be our turn.

lettergram 4y ago
The challenge with genetics research is it could also result in the death of every human on the planet. It’s an amazing power for good and bad.
- sinenomine 4y ago
  You don't need to ban, say, clinical trials of gene therapy (especially with inert lipid nanoparticle carriers which do not replicate), to ban a quite narrow and not really clinically useful subfield called "gain of function research". Why can't our legal system deter the obvious high-level publicly visible perpetrators of the recent "gain-of-function" fiasco is really some food for thought.
  - shadowgovt 4y ago
    As a general rule, we don't arrest people for things that aren't illegal. ... Unless by "deter" you just meant "make it illegal," in which case, agreed.
  - lettergram 4y ago
    It’s more than broad weaponization of viruses that are a danger though. Take for instance what we’re doing with plants. We make designer plants that provide food, and are immune from particular pesticides. We then spray the fields and all the other plants and bugs die (besides the immune plants). What happens when it turns out some genetic inserts in the corn creates something like mad cow disease (but in humans) 3-5 years later? Turns out some protein the corn produced we thought was harmless caused massive issues. Genetics has massive implications even if well meaning. I think the ability to eliminate disease is massively powerful and a net good. That said, I’m concerned about the long term tail end risks of such work. I don’t think you can ban it, because someone will do the work. And those that do the work will get a competitive advantage (eventually letting them “win”). I think it’s about mitigating risks by reducing / limiting mass adoption of genetic based technology without a very long window of analysis.