8 ms·

This is to be expected. Any time we do any transplant immunosupressants are given to the recipient for the rest of their life, but this only slows the inevitabl

This is to be expected. Any time we do any transplant immunosupressants are given to the recipient for the rest of their life, but this only slows the inevitable. Heart transplants recipients all get accelerated atherosclerosis. Lung transplant recipients all get long term fibrosis. We buy time with these procedures and do everything we can to keep them going, but if you have a transplant, you're in a really bad spot to begin with.

FreeFull 7y ago
I wonder how long it will take until growing organs from the recipient's own stem cells is actually viable. There definitely is some interesting research, and it would completely circumvent the problems with the immune system.
- markkat 7y ago
  This issue is why I started Forever Labs (YCS17). We bank your stem cells. Immunity presents many difficult problems to be solved. I’d rather worry about the therapeutic developments alone rather than add immunity on top of it.
  - puranjay 7y ago
    I'm a little curious how something like this works within the economic framework of a startup. How do you reconcile the inherently long-term nature of your business (I might need my stem cells in a decade or two) with the inherent instability of a startup (you might go out of business within 3 years)?
    - markkat 7y ago
      The annual storage fees ($250/yr) cover our banking costs. The banking needs little more than invoicing to remain viable, and with the numbers we have banked, it could survive as a stand-alone entity, or would be an asset that could be acquired by another banking service. My cells are in there, as are those of many of my family members. I want them available 20 years from now. Of course, we aspire to mature beyond a startup, and are getting there. :)
      - sushid 7y ago
        What is the value prop for extracting and storing stem cells now vs. extracting them later? Is it just that you’ll have to extract less bone marrow now vs later? Isn’t there a decline in quality and quantity of viable stem cells when they’re stored?
        markkat 7y ago
        There's actually a significant decline in quality and quantity that continues with age. That's why we cryopreserve them. If brought down to liquid nitrogen temp properly, they can remain viable nearly indefinitely.
bobwaycott 7y ago
Thanks for this. I had no idea this was the case, and have long operated under the erroneous belief that most transplants basically worked and left the recipient relatively problem-free afterward—well, at least as far as the transplant was concerned. It is odd to learn that transplants are a time-buying exercise.
peterlk 7y ago
I just finished up an introductory biology lecture series, and this suddenly makes less sense to me than it did before. What is it about the foreign cells that is identified as foreign by the host cells? The cells ought to be remarkably similar. They're human, with the same function/pluripotency using the same protein interactions. So why attack it?
- ceejayoz 7y ago
  There's a lot more to immune response than "does this look like a human cell?" See, for example, blood types, where giving an A type person B type blood will cause serious issues. Each human has a largely unique signature of HLAs (https://en.wikipedia.org/wiki/Human_leukocyte_antigen https://en.wikipedia.org/wiki/Human_leukocyte_antigen).
  - cabalamat 7y ago
    The whole point of this, evolutionarily, is so that a parasite that thrived in one human body won't necessarily thrive in another. This is also why many species reproduce by sex.
- Enginerrrd 7y ago
  Because it's part of the arms race with pathogens that has been going on for a billion years since multi-cellular life first appeared. Pathogens do lots of very clever things to hide from the immune system, so the immune system is tuned to detect very subtle changes. The body largely operates on zero-trust network models, except for a few locations where the benefit of a too-active immune system has serious consequences to the fitness of the organism. The eyes and the testicles are good examples of that in humans.
  - asveikau 7y ago
    I guess auto-immune disease is an example of where it also goes the wrong way for somebody. Probably most of us know somebody with IBD, lupus, or any of the others. It's very common for the body to reject something benign, or ourselves.
johnmaguire2013 7y ago
> Any time we do any transplant immunosupressants are given to the recipient for the rest of their life, but this only slows the inevitable. Is this true that it is inevitable? My understanding, from my girlfriend attending medical school (only M1), is that for many types of transplants, when immunosupressants are taken properly, it is unlikely that the organ will ever be rejected. For example, only 10-20% of patients who receive a kidney transplant will experience rejection[1]. [1] https://columbiasurgery.org/kidney-transplant/organ-rejection-after-renal-transplant https://columbiasurgery.org/kidney-transplant/organ-rejectio...
- arkades 7y ago
  “Only 20%” and “unlikely to ever be rejected” are worlds apart. Modern immunosuppressive therapy for, for instance kidneys, has dropped the five year acute rejection rate from 50% to 20%. About 8-10% in the first year. You can get a 5% 10-year non-rejection rate only in the most hand-picked groups (adheres to meds, no underlying systemic disease, and no chronic nephropathy). That sub-population exists, but it’s pretty uncommon.
  - sandworm101 7y ago
    People without underlying disease generally dont need or get replacement organs. These are all complex cases. Only in the most rare of circumstances does an otherwise totally healthy person need a new kidney.
    - capnslowish 7y ago
      Focal glomerulosclerosis destroys kidneys in a completely healthy person.
  - johnmaguire2013 7y ago
    > “Only 20%” and “unlikely to ever be rejected” are worlds apart. The parent comment I responded to stated it was "inevitable." "Inevitable" and "only 20%" are many more worlds apart than "unlikely to ever be rejected" and "only 20%". "Unlikely" is a bit subjective, but it is well below a coin flip. I cited a source for the statistics. If you disagree, can you please cite your source?
ravar 7y ago
I recently listened to this podcast. https://news.ycombinator.com/item?id=21051174 https://news.ycombinator.com/item?id=21051174 It is about widespread fraud in the drug industry. During the interview it was mentioned that some people are seeing organ failure due getting fraudulent drugs from abroad. It is possible that this is not what happened in this case, but it seems plausible. To anyone who has the time, listen to this podcast. It was really educational and scary, pharmaceuticals fraud is no joke. *The interview discusses the material in Katherine Eban's book Bottle of Lies.
- Avamander 7y ago
  Interestingly the EU is working on building a verification service for pharmaceuticals but some countries are pushing back.
- zaroth 7y ago
  The human brain is wired to make connections, but it's important to step back and realize the universe of "plausible" explanations are almost infinite. It is nothing more than rank speculation that these two stories are somehow related. The world is teeming with junk science like this, and it can be dangerous and even fatal. (E.g. anti-vexers). That's why I think it's important to recognize it when you see it, and call it out. Even more-so if you find yourself possibly espousing damaging speculation without a scintilla of evidence.
  - ravar 7y ago
    The evidence is the podcast/interview. It is not known the extent to which generic drugs are affected. But in almost all the Indian plans investigated there was evidence of fraud, and I believe evidence of fraud was found in 80% of Chinese generic pharmaceutical plants. Additionally according to the author of the book there have already been cases of organ rejections due to fraudulent generics. Before dismissing my comments out of hand maybe you should look at my evidence.
    - jiveturkey 7y ago
      I'm sorry but GP is completely correct and you are just reacting defensively. He didn't claim that your evidence was faulty, but that there is nothing to connect these two stories. You're making a link that does not exist. In fact, when you say > It is possible that this is not what happened you are making it seem quite likely that this is indeed what happened. With no supporting evidence. It's exactly what anti-vaxers do.
Pete_D 7y ago
How much of this is mitigated by donor/recipient compatibility (haplotypes? is that the right word?)? Is there no such thing as a purely compatible donor?
- robbiep 7y ago
  A 100% compatible donor is a identical twin or clone. Besides the MHC haplotypes which govern large parts of the immune response to ‘self’ there is the actual makeup of the rest of the genetic material which may be presented as antigens and then recognised as foreign
- pkaye 7y ago
  Yes identical twins are fully compatible. The first kidney transplant was done between identical twins and the the recipient lived with no anti-rejection medications for decades from what I recall.
- Medicalidiot 7y ago
  There have been instances of kidney transplants between identical twins to withdraw immunosuppressants after some time.
Apofis 7y ago
Absolutely terrible that's happening, though. Hopefully with further genetic research and being able to grow new organs, these issues will go away.

FreeFull 7y ago

I wonder how long it will take until growing organs from the recipient's own stem cells is actually viable. There definitely is some interesting research, and it would completely circumvent the problems with the immune system.

markkat 7y ago
This issue is why I started Forever Labs (YCS17). We bank your stem cells. Immunity presents many difficult problems to be solved. I’d rather worry about the therapeutic developments alone rather than add immunity on top of it.
- puranjay 7y ago
  I'm a little curious how something like this works within the economic framework of a startup. How do you reconcile the inherently long-term nature of your business (I might need my stem cells in a decade or two) with the inherent instability of a startup (you might go out of business within 3 years)?
  - markkat 7y ago
    The annual storage fees ($250/yr) cover our banking costs. The banking needs little more than invoicing to remain viable, and with the numbers we have banked, it could survive as a stand-alone entity, or would be an asset that could be acquired by another banking service. My cells are in there, as are those of many of my family members. I want them available 20 years from now. Of course, we aspire to mature beyond a startup, and are getting there. :)
    - sushid 7y ago
      What is the value prop for extracting and storing stem cells now vs. extracting them later? Is it just that you’ll have to extract less bone marrow now vs later? Isn’t there a decline in quality and quantity of viable stem cells when they’re stored?
      - markkat 7y ago
        There's actually a significant decline in quality and quantity that continues with age. That's why we cryopreserve them. If brought down to liquid nitrogen temp properly, they can remain viable nearly indefinitely.

bobwaycott 7y ago

Thanks for this. I had no idea this was the case, and have long operated under the erroneous belief that most transplants basically worked and left the recipient relatively problem-free afterward—well, at least as far as the transplant was concerned. It is odd to learn that transplants are a time-buying exercise.

peterlk 7y ago

I just finished up an introductory biology lecture series, and this suddenly makes less sense to me than it did before. What is it about the foreign cells that is identified as foreign by the host cells? The cells ought to be remarkably similar. They're human, with the same function/pluripotency using the same protein interactions. So why attack it?

ceejayoz 7y ago
There's a lot more to immune response than "does this look like a human cell?" See, for example, blood types, where giving an A type person B type blood will cause serious issues. Each human has a largely unique signature of HLAs (https://en.wikipedia.org/wiki/Human_leukocyte_antigen https://en.wikipedia.org/wiki/Human_leukocyte_antigen).
- cabalamat 7y ago
  The whole point of this, evolutionarily, is so that a parasite that thrived in one human body won't necessarily thrive in another. This is also why many species reproduce by sex.
Enginerrrd 7y ago
Because it's part of the arms race with pathogens that has been going on for a billion years since multi-cellular life first appeared. Pathogens do lots of very clever things to hide from the immune system, so the immune system is tuned to detect very subtle changes. The body largely operates on zero-trust network models, except for a few locations where the benefit of a too-active immune system has serious consequences to the fitness of the organism. The eyes and the testicles are good examples of that in humans.
- asveikau 7y ago
  I guess auto-immune disease is an example of where it also goes the wrong way for somebody. Probably most of us know somebody with IBD, lupus, or any of the others. It's very common for the body to reject something benign, or ourselves.

johnmaguire2013 7y ago

> Any time we do any transplant immunosupressants are given to the recipient for the rest of their life, but this only slows the inevitable. Is this true that it is inevitable? My understanding, from my girlfriend attending medical school (only M1), is that for many types of transplants, when immunosupressants are taken properly, it is unlikely that the organ will ever be rejected. For example, only 10-20% of patients who receive a kidney transplant will experience rejection[1]. [1] https://columbiasurgery.org/kidney-transplant/organ-rejection-after-renal-transplant https://columbiasurgery.org/kidney-transplant/organ-rejectio...

arkades 7y ago
“Only 20%” and “unlikely to ever be rejected” are worlds apart. Modern immunosuppressive therapy for, for instance kidneys, has dropped the five year acute rejection rate from 50% to 20%. About 8-10% in the first year. You can get a 5% 10-year non-rejection rate only in the most hand-picked groups (adheres to meds, no underlying systemic disease, and no chronic nephropathy). That sub-population exists, but it’s pretty uncommon.
- sandworm101 7y ago
  People without underlying disease generally dont need or get replacement organs. These are all complex cases. Only in the most rare of circumstances does an otherwise totally healthy person need a new kidney.
  - capnslowish 7y ago
    Focal glomerulosclerosis destroys kidneys in a completely healthy person.
- johnmaguire2013 7y ago
  > “Only 20%” and “unlikely to ever be rejected” are worlds apart. The parent comment I responded to stated it was "inevitable." "Inevitable" and "only 20%" are many more worlds apart than "unlikely to ever be rejected" and "only 20%". "Unlikely" is a bit subjective, but it is well below a coin flip. I cited a source for the statistics. If you disagree, can you please cite your source?

ravar 7y ago

I recently listened to this podcast. https://news.ycombinator.com/item?id=21051174 https://news.ycombinator.com/item?id=21051174 It is about widespread fraud in the drug industry. During the interview it was mentioned that some people are seeing organ failure due getting fraudulent drugs from abroad. It is possible that this is not what happened in this case, but it seems plausible. To anyone who has the time, listen to this podcast. It was really educational and scary, pharmaceuticals fraud is no joke. *The interview discusses the material in Katherine Eban's book Bottle of Lies.

Avamander 7y ago
Interestingly the EU is working on building a verification service for pharmaceuticals but some countries are pushing back.
zaroth 7y ago
The human brain is wired to make connections, but it's important to step back and realize the universe of "plausible" explanations are almost infinite. It is nothing more than rank speculation that these two stories are somehow related. The world is teeming with junk science like this, and it can be dangerous and even fatal. (E.g. anti-vexers). That's why I think it's important to recognize it when you see it, and call it out. Even more-so if you find yourself possibly espousing damaging speculation without a scintilla of evidence.
- ravar 7y ago
  The evidence is the podcast/interview. It is not known the extent to which generic drugs are affected. But in almost all the Indian plans investigated there was evidence of fraud, and I believe evidence of fraud was found in 80% of Chinese generic pharmaceutical plants. Additionally according to the author of the book there have already been cases of organ rejections due to fraudulent generics. Before dismissing my comments out of hand maybe you should look at my evidence.
  - jiveturkey 7y ago
    I'm sorry but GP is completely correct and you are just reacting defensively. He didn't claim that your evidence was faulty, but that there is nothing to connect these two stories. You're making a link that does not exist. In fact, when you say > It is possible that this is not what happened you are making it seem quite likely that this is indeed what happened. With no supporting evidence. It's exactly what anti-vaxers do.

Pete_D 7y ago

How much of this is mitigated by donor/recipient compatibility (haplotypes? is that the right word?)? Is there no such thing as a purely compatible donor?

robbiep 7y ago
A 100% compatible donor is a identical twin or clone. Besides the MHC haplotypes which govern large parts of the immune response to ‘self’ there is the actual makeup of the rest of the genetic material which may be presented as antigens and then recognised as foreign
pkaye 7y ago
Yes identical twins are fully compatible. The first kidney transplant was done between identical twins and the the recipient lived with no anti-rejection medications for decades from what I recall.
Medicalidiot 7y ago
There have been instances of kidney transplants between identical twins to withdraw immunosuppressants after some time.

Apofis 7y ago

Absolutely terrible that's happening, though. Hopefully with further genetic research and being able to grow new organs, these issues will go away.