It’s pretty wild being alive these days. Lots of big stuff the species is struggling to adapt to and figure out how to exist with.
But also… we got the tablets from Star Trek. And now we have the ship’s computer from Star Trek, and the early makings of the holodeck. And we’re making pigmen senior citizens who would otherwise be dead.
It’s quite something to stop and think about how the problem is becoming less and less about “how do we do the science and the engineering?” And more about “how do we handle how this changes what it is like to be human today?”
Keep in mind the amazing thing is the survival of having the transplant in addition to kidney failure. People have been living up to five years without kidneys by relying on dialysis.
I was just thinking about heart transplants and how they’re treated as commonplace now, but they are nuts when you think about them.
You can hook up the nerve wires and blood pipes from one body into the heart from another body and it works? Just thinking about the simple physical connections would make me nervous. Why isn’t there blood just leaking out in your body? Why isn’t that other heart sliding out of place while you move around?
I have always wondered what decision I would make facing such a health concern.
> Reaching 12 months would be another milestone and a “fantastic long-term outcome”, he adds.
I am surprised by this being considered a long-term outcome though. Going through the high risk of a kidney transplant, immunosuppression required, risk of using a pig kidney in general, etc seems like a lot if the hope is for 12 months as a long-term unlikelihood.
I remember interviewing for a bioinformatics role at a certain San Diego company 8 years ago and being told by the staff they were working on humanizing pig kidneys.
I thought it was a fucking insane idea and wanted to leave immediately.
It is fucking wild that we need to resort to putting pig kidneys into humans to squeeze out a few more months of life, while tens of millions of perfectly good human organs are burned or left to rot in the ground each year.
Richard Slayman was a pioneer. He made an amazing decision, to see if it could be done. This was hard work done through eGenesis, and the steps to get to this point is quite interesting.
>> First, the donors were often created on a commercial pig breed whose heart and kidney sizes are too large for human application. Although elimination of growth hormone receptor gene expression could reduce organ sizes, it comes with other undesired biological consequences. Second, the donors were designed for testing in OWMs. They lacked the α-Gal (galactose-α-1,3-galactose) or the α-Gal and Sd(a) (Sia-α2.3-[GalNAc-β1.4]Gal-β1.4-GlcNAc) glycans but expressed the Neu5Gc (N-glycolylneuraminic acid) glycan to match with Neu5Gc expression in OWMs. However, in vitro analysis suggests that a human-compatible porcine donor should ideally have all three glycans eliminated to match with the absence of the three glycans in humans. Although renal grafts derived from the porcine donors lacking these three glycans and carrying various human transgenes have been tested in OWMs, graft survival was short8 or not all human transgenes were expressed. Third, the donors carried porcine endogenous retrovirus (PERV) sequences in their genome, which present a zoonotic risk, as PERV transmission to human cells in culture and their integration into the human genome have been demonstrated.
Transplanted kidneys get rejected by the recipient's immune system eventually, you'd really need to clone the kidney from the individual's DNA to solve the rejection problem. There's also been some success with integrating the DNA from the kidney donor (a human) into the recipient's bone marrow to stop the rejection process, but I hear it can be a brutal procedure in which the original bone marrow must be destroyed using chemotherapy or radiation.
If this becomes commonplace and animals are bred/raised just for their organs, we get into murky ethical territory. (Yes, people already eat the organs for food, that's murky too. But industrial scale organ farming sounds even worse somehow.)
That's genuinely impressive. Six months without dialysis after a xenotransplant is no small milestone, especially considering how many hurdles this field has faced over the years. The level of genetic modification involved shows how far biotech has come. Still, it's hard not to wonder about the long game. Immunosuppression, organ longevity, possible unforeseen complications - all big unknowns
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[ 2.6 ms ] story [ 43.4 ms ] threadIt’s pretty wild being alive these days. Lots of big stuff the species is struggling to adapt to and figure out how to exist with.
But also… we got the tablets from Star Trek. And now we have the ship’s computer from Star Trek, and the early makings of the holodeck. And we’re making pigmen senior citizens who would otherwise be dead.
It’s quite something to stop and think about how the problem is becoming less and less about “how do we do the science and the engineering?” And more about “how do we handle how this changes what it is like to be human today?”
https://www.youtube.com/watch?v=PwQns6vGfj4&list=PL4NL9i-Fu1...
You can hook up the nerve wires and blood pipes from one body into the heart from another body and it works? Just thinking about the simple physical connections would make me nervous. Why isn’t there blood just leaking out in your body? Why isn’t that other heart sliding out of place while you move around?
> Reaching 12 months would be another milestone and a “fantastic long-term outcome”, he adds.
I am surprised by this being considered a long-term outcome though. Going through the high risk of a kidney transplant, immunosuppression required, risk of using a pig kidney in general, etc seems like a lot if the hope is for 12 months as a long-term unlikelihood.
I thought it was a fucking insane idea and wanted to leave immediately.
Turns out I am a fool.
>> First, the donors were often created on a commercial pig breed whose heart and kidney sizes are too large for human application. Although elimination of growth hormone receptor gene expression could reduce organ sizes, it comes with other undesired biological consequences. Second, the donors were designed for testing in OWMs. They lacked the α-Gal (galactose-α-1,3-galactose) or the α-Gal and Sd(a) (Sia-α2.3-[GalNAc-β1.4]Gal-β1.4-GlcNAc) glycans but expressed the Neu5Gc (N-glycolylneuraminic acid) glycan to match with Neu5Gc expression in OWMs. However, in vitro analysis suggests that a human-compatible porcine donor should ideally have all three glycans eliminated to match with the absence of the three glycans in humans. Although renal grafts derived from the porcine donors lacking these three glycans and carrying various human transgenes have been tested in OWMs, graft survival was short8 or not all human transgenes were expressed. Third, the donors carried porcine endogenous retrovirus (PERV) sequences in their genome, which present a zoonotic risk, as PERV transmission to human cells in culture and their integration into the human genome have been demonstrated.
https://www.nature.com/articles/s41586-023-06594-4
https://en.wikipedia.org/wiki/Richard_Slayman
https://newsnetwork.mayoclinic.org/discussion/video-eliminat...
https://www.immunofree.com/how-it-works/
If I were a patient, I'd probably want a pig kidney now and really hope it lasts until something like kidney cloning is a thing.
https://www.science.org/content/article/longest-human-transp...
Pretty amazing tech tbh
If this becomes commonplace and animals are bred/raised just for their organs, we get into murky ethical territory. (Yes, people already eat the organs for food, that's murky too. But industrial scale organ farming sounds even worse somehow.)