Extremely interesting first step, one that suggests that there is quite a long way yet to go before the rejection issue is resolved. {And as a non-medical person, I though that the procedure used was somewhat creepy, even though all ethical norms were observed. )
I agree, there is likely a long way to go before we have xenogeneic transplants figured out. However, one huge silver lining that I failed to emphasize in the article is the significant advancements in gene editing technology that have made the Alpha-Gal pig possible in the first place. Now that these gene editing tools have become so efficient and affordable for producing targeted edits, I expect the march of progress to speed up.
Being given a pig organ does sound creepy. It reflects the dire straits of people waiting on the transplant list, where no other options are available. Perhaps someday we will figure out how to produce a tissue-engineered kidney as an alternative.
Very interesting article about a promising application of gene editing technology.
Still, researchers keep trying to force the square peg of xenotransplantation into the round hole of human biology. Wouldn't it be easier, faster, and make more sense to remove one of the biggest barriers to organ shortages by letting people sell them? Thousands of people on transplant lists die every year, deaths that might very well be prevented if the prohibition on sales were lifted. Of course as soon as you say that people assume that orphans will be selling their hearts on street corners, but there's no reason for that to be the case, especially if the sold organs had to come from patients declared legally dead, just as donated organs do. And when it comes to being not-for-the-squeamish, how is signing a card to authorize the post mortem sale of your heart any creepier than keeping someone on life support for a month so he can be experimented on? The researchers' experimentation was handled ethically and, I imagine, with kindness toward the family that approved it. The sale of a brain-dead patient's organs wouldn't be any different. Better, in fact: If the seller had designated the sale in advance, in writing, just as people do now with donations, then the "organ seller card" could specify who benefited from the sale: a charity, a family member, the person's estate; it could be applied toward the deceased's funeral expenses or hospital bill. That additional financial incentive might be enough to convince another 6,000 Americans to sign up for the program: enough to save the 6,000 people who die on waiting lists every year.
Hi Fager, you raise some compelling points about potentially alleviating the organ shortage crisis through the legalization of organ sales. It's hard to argue with this if you truly believe in the principles of bodily autonomy. Furthermore, there is the potential option of having organ sales act as a form of life insurance. It could provide significant support for a donor's family in the event of their untimely passing.
Your comment reminds me of an interesting article on Astral Codex Ten (linked below), where the author discusses the development of incentives for organ donations. In the short term these strategies would be extremely beneficial. However, there are significant drawbacks even beyond any ethical implications of such a system, particularly the lifelong need for recipients to take immunosuppressant drugs. These donor organs are only a temporary bandaid.
I think the development of genetically modified organs will be necessary regardless if the source is from animals, tissue engineered, or a human donor.
So the end goal of xenotransplantation using genetically modified organs is to eliminate the need to take anti-rejection drugs at all? But the researchers had to use immunosuppressants with the alpha-gal kidney. I guess it's still a major advance if it required less of them, or safer types, if there is such a thing. Years ago I had a young cat with kidney failure who got a transplant at UW-Madison, and he was on cyclosporin for the rest of his life. (I also ended up with a bonus additional cat; part of the deal was that you take responsibility for the donor cat, who gave up just one kidney. Good thing that's not a requirement for human recipients. Personally I'd rather die of organ failure than take someone else home from the hospital with me.)
Offering tax credits to encourage donation is a great idea, but I still think the selling-organs proponents would get farther faster if they started with a transitional step of deceased sellers: For people who already accept the idea of deceased donors it would probably be easier to accept the idea of deceased sellers. If the priority is to start saving as many lives as possible as soon as possible, then undermining the resistance to organ sales in stages might be the fastest way to get there. Ethically I think the only real question is whether individual bodily autonomy is upheld as a value: Can I do whatever I want with my organs and my life, or not? If someone doesn't have the right to bodily autonomy, how can someone else, who also lacks the right to decide for himself, claim the right to decide for him? It makes no sense morally.
The ultimate goal of xenotransplantation (at least from Revivicor) is indeed to maximize compatibility and even eliminate the need for immunosuppressants. This specific model with the single alpha-gal knock out was just a step along the way (although I'm sure they would have taken the win if it were that simple). They have a newer pigs with 9 additional edits (10 edited genes total), three of these genes are knockouts to prevent rejection, one knockout to limit organ growth after transplantation, and six human genes were inserted to increase compatibility (https://www.revivicor.com/technologies/). I think there is a good chance additional edits and work is required before we reach that goal.
I agree with you on having to take home a stranger. But what about a pig ? (;
On the organ sales front, starting with deceased sellers does seem like a smart first move. It's like easing into the whole idea of financial incentives for organ donation. However, I am not very optimistic. I think bureaucrats have effectively captured many of our medical institutions and have made them unchangeable. I was working in a startup with an ongoing clinical trial and we could not give meaningful incentives to recruit candidates.
Extremely interesting first step, one that suggests that there is quite a long way yet to go before the rejection issue is resolved. {And as a non-medical person, I though that the procedure used was somewhat creepy, even though all ethical norms were observed. )
I agree, there is likely a long way to go before we have xenogeneic transplants figured out. However, one huge silver lining that I failed to emphasize in the article is the significant advancements in gene editing technology that have made the Alpha-Gal pig possible in the first place. Now that these gene editing tools have become so efficient and affordable for producing targeted edits, I expect the march of progress to speed up.
Being given a pig organ does sound creepy. It reflects the dire straits of people waiting on the transplant list, where no other options are available. Perhaps someday we will figure out how to produce a tissue-engineered kidney as an alternative.
Very interesting article about a promising application of gene editing technology.
Still, researchers keep trying to force the square peg of xenotransplantation into the round hole of human biology. Wouldn't it be easier, faster, and make more sense to remove one of the biggest barriers to organ shortages by letting people sell them? Thousands of people on transplant lists die every year, deaths that might very well be prevented if the prohibition on sales were lifted. Of course as soon as you say that people assume that orphans will be selling their hearts on street corners, but there's no reason for that to be the case, especially if the sold organs had to come from patients declared legally dead, just as donated organs do. And when it comes to being not-for-the-squeamish, how is signing a card to authorize the post mortem sale of your heart any creepier than keeping someone on life support for a month so he can be experimented on? The researchers' experimentation was handled ethically and, I imagine, with kindness toward the family that approved it. The sale of a brain-dead patient's organs wouldn't be any different. Better, in fact: If the seller had designated the sale in advance, in writing, just as people do now with donations, then the "organ seller card" could specify who benefited from the sale: a charity, a family member, the person's estate; it could be applied toward the deceased's funeral expenses or hospital bill. That additional financial incentive might be enough to convince another 6,000 Americans to sign up for the program: enough to save the 6,000 people who die on waiting lists every year.
Hi Fager, you raise some compelling points about potentially alleviating the organ shortage crisis through the legalization of organ sales. It's hard to argue with this if you truly believe in the principles of bodily autonomy. Furthermore, there is the potential option of having organ sales act as a form of life insurance. It could provide significant support for a donor's family in the event of their untimely passing.
Your comment reminds me of an interesting article on Astral Codex Ten (linked below), where the author discusses the development of incentives for organ donations. In the short term these strategies would be extremely beneficial. However, there are significant drawbacks even beyond any ethical implications of such a system, particularly the lifelong need for recipients to take immunosuppressant drugs. These donor organs are only a temporary bandaid.
I think the development of genetically modified organs will be necessary regardless if the source is from animals, tissue engineered, or a human donor.
https://www.astralcodexten.com/p/my-left-kidney
So the end goal of xenotransplantation using genetically modified organs is to eliminate the need to take anti-rejection drugs at all? But the researchers had to use immunosuppressants with the alpha-gal kidney. I guess it's still a major advance if it required less of them, or safer types, if there is such a thing. Years ago I had a young cat with kidney failure who got a transplant at UW-Madison, and he was on cyclosporin for the rest of his life. (I also ended up with a bonus additional cat; part of the deal was that you take responsibility for the donor cat, who gave up just one kidney. Good thing that's not a requirement for human recipients. Personally I'd rather die of organ failure than take someone else home from the hospital with me.)
Offering tax credits to encourage donation is a great idea, but I still think the selling-organs proponents would get farther faster if they started with a transitional step of deceased sellers: For people who already accept the idea of deceased donors it would probably be easier to accept the idea of deceased sellers. If the priority is to start saving as many lives as possible as soon as possible, then undermining the resistance to organ sales in stages might be the fastest way to get there. Ethically I think the only real question is whether individual bodily autonomy is upheld as a value: Can I do whatever I want with my organs and my life, or not? If someone doesn't have the right to bodily autonomy, how can someone else, who also lacks the right to decide for himself, claim the right to decide for him? It makes no sense morally.
The ultimate goal of xenotransplantation (at least from Revivicor) is indeed to maximize compatibility and even eliminate the need for immunosuppressants. This specific model with the single alpha-gal knock out was just a step along the way (although I'm sure they would have taken the win if it were that simple). They have a newer pigs with 9 additional edits (10 edited genes total), three of these genes are knockouts to prevent rejection, one knockout to limit organ growth after transplantation, and six human genes were inserted to increase compatibility (https://www.revivicor.com/technologies/). I think there is a good chance additional edits and work is required before we reach that goal.
I agree with you on having to take home a stranger. But what about a pig ? (;
On the organ sales front, starting with deceased sellers does seem like a smart first move. It's like easing into the whole idea of financial incentives for organ donation. However, I am not very optimistic. I think bureaucrats have effectively captured many of our medical institutions and have made them unchangeable. I was working in a startup with an ongoing clinical trial and we could not give meaningful incentives to recruit candidates.
Pigs seem to be equally as tasty as they are useful. Praise the pig!