First Xenotransplantation of Engineered Porcine Organs to Human Patients
Sourcing organs from genetically engineered pigs is one of the options under development for the production of organs on demand for patients who need transplants. Ethically, growing organs from cells would be a better option, but we live in a world in which animals are widely seen only as tools to be used and consumed; one might hope that our descendants will grow to be better than us in that regard. Major surgery is a high risk undertaking in older people, and the best of all options would be to find ways to spur controlled regrowth and repair in native tissues. That remains more of an aspirational goal at this point, and engineered pigs already exist. Following on from a test of kidney transplants from pigs to brain-dead patients, researchers recently successfully transplanted an engineered porcine heart into a conscious human patient.
The first person to receive a transplanted heart from a genetically modified pig is doing well after the procedure. Physicians and scientists worldwide have for decades been pursuing the goal of transplanting animal organs into people, known as xenotransplantation. Last week's procedure marks the first time that a pig organ has been transplanted into a human who has a chance to survive and recover. In 2021, surgeons transplanted kidneys from the same line of genetically modified pigs into two legally dead people with no discernible brain function. The organs were not rejected, and functioned normally while the deceased recipients were sustained on ventilators.
Xenotransplantation has seen significant advances in recent years with the advent of CRISPR-Cas9 genome editing, which made it easier to create pig organs that are less likely to be attacked by human immune systems. The latest transplant used organs from pigs with ten genetic modifications. The researchers had applied to the US Food and Drug Administration (FDA) to do a clinical trial of the pig hearts in people, but were turned down. The agency was concerned about ensuring that the pigs came from a medical-grade facility and wanted the researchers to transplant the hearts into ten baboons before moving on to people.
But a 57-year-old patient team a chance to jump straight to a human transplant. The patient had been on cardiac support for almost two months and couldn't receive a mechanical heart pump because of an irregular heart beat. Neither could he receive a human transplant, because he had a history of not complying with doctors' treatment instructions. Given that he otherwise faced certain death, the researchers got permission from the FDA to give the patient a pig heart.
For now, transplantation is limited by the supply of pigs as well as regulatory hurdles. There is currently just one company - Revivicor, owned by United Therapeutics - that has suitable facilities and clinical-grade pigs. To make the pig heart used in the transplant, the company knocked out three pig genes that trigger attacks from the human immune system, and added six human genes that help the body to accept the organ. A final modification aims to prevent the heart from responding to growth hormones, ensuring that organs from the 400-kilogram animals remain human-sized.
Martine Rothblatt has done such amazing work investing and leading this front and it has truly matured over the last decade where these whole organ xeno options are a reality in 2022!
Other approaches have been spinning their wheels and very little clinical advances have come from bio-printing organs and related tools
Say what you will but there are tens of thousands of patients in end stage organ failure who can benefit from these tool today...
I don't get the anti-aging context? How does this help?
I hoped that organs would come before meat but now with organisations like New Harvest, meat seems to come first. But when accepted by people organ would be easier to accept.
Please note that all the statements about "there is no rejection" doesn't mean the heart is fully immuno-compatible. The patient will be on powerful and novel immunosupressants. Some of them are half of he success story. While there were a lot of genetic modifications to reduce the rejections it didn't make it 100% compatible. Please see this article : https://www.science.org/content/article/here-s-how-scientists-pulled-first-pig-human-heart-transplant
Even with the modifications to the heart, to prevent rejection, the UMSOM team is giving Bennett a strong immunosuppressant: an experimental antibody drug called KPL-404, made by Kiniksa Pharmaceuticals, Ltd.
Standard immunosuppressants used in human-to-human organ transplants aren't effective if the immune system makes lots of antibodies against the organ, as surgeons feared would be the case with the pig heart. KPL-404 shuts down production of these antibodies by binding to a cellular receptor called CD40, suppressing the activity of antibody-producing B cells, and inhibiting their cross-talk with T cells that coordinate the immune system's response to an invader. "The 10 [altered] genes help, but the anti-CD40 antibody, which had been my main focus throughout my career, I think is the game changer," Mohiuddin says.
Kiniksa has been working on KPL-404 as a treatment for rheumatoid arthritis and announced positive results from a safety trial in healthy volunteers in May 2021.
@JonesI
The rejuvenation can be done one organ at a time :)
At least in theory. If the approach works without life-long ummnosupression (not yet the case) then there are a whole bunch of organs which get beating of the age. If you replace them, you will solve or alleviate a lot of conditions. While not a simple procedure, there is a clear research and investment path to clinical applications. And, eventually, you could be able to repair/replace every single organ, except the brain. There are huge hurdles on spinal cord and eye nerves, at least for now.
@Cuberat
Who cares about immuno-suppression - that is the case for human-human organ transplants too
There are thousands waiting for human organs who will die in the process
This is a great way to bridge the gap and save many lives today
@Jim Taylor: You're correct but this a novel immunosuppressant. Patients are accepting this and its going to be big business. But it has taken a long time. I remember reading an article in 1999 that it were not more then 5y in future.
@cuberat
'The rejuvenation can be done one organ at a time :)'
Hm... if you stitch an old mouse and a young mouse together... the old mouse gets younger, the young mouse gets older. Parabiosis... and all that.
If you stitch a 'young' organ into an old body... what happens?
@Jim Taylor
there's a big difference if you have a 100% compatible organ. After a few months of recovery you could be as good as new. And here you have to live with half of your immune system off. A good tradeoff if you have no other choice except dying, but not a long-term solution.
@Jones
I guess it depends on organs, whole body conditions and such. But let's say that you have scarring in the heart due to some neglected heart attack. Once you clean the main vains, or havea bypass you are not back to normla, the heart is damaged. If you repalce it with 100% bio/immunocompatible organ it will work as even before the heart attack. It might have an accelerated aging and reach the whole body average age sooner. But for the time being it will be "young" . Ultimately, we will have to try and see. I guess for some organs it will be a 90% young, and others will get old quickly. Until very recently it was all theoretical and now we have the practical, albeit extremely difficult , way of trying it.
Just as it's better to eat bacon from well treated pastured pigs rather than eat those that were raised in horrible feed lots and cages, we would hope the pig that gives us a heart is treated well in life and killed mercifully. Virginia Tech here in Blacksburg treats animals well and it's highly likely that the pig who gave his life so that man could live was treated royally.
More about this here:
https://roanoke.com/news/local/blacksburg-company-raised-genetically-modified-pig-for-first-heart-transplant-into-human/article_7789edac-73e9-11ec-b000-eb28e2a5031b.html
Xenotransplantation is developing faster then 4D bioprinting. Im a vegan and against killing pigs for organs but would said yes if I were dying. See the developments taking place at company egenesis. Im going to invest when they have IPO. Either stocks in company or via ETF - ARKG.
@tom.a
Yes - I wholeheartedly agree
I'm not big on killing sentient animals, but this really has begun to be a game changer
I always thought the bio-printing folks would succeed and xeno would fade away
But I think now the reverse
Xeno is here to stay
Hi Cuberat! Just a 2 cents.
I too am of the same opinion, that, I mean a pig's heart saved an older man's life, thus it is extremely valuable (his life, saved by the pig's heart); this, is incredible news...but, like you said, I believe too it is a temporary solution, a better-than-dead-tradeoff and as you said, not a long term solution. It's incredible that he is alive, thank to the pig animal's heart. We always thought this would be impossible; but, as you said, this whole 'needing to suppress the immune system' to avoid organ rejection is scary...I mean it's far scary him being dead from his heart failed totally, than having to suppress his immune system due to animal organ/invader rejection by immune system..it's just, as you said, temporary solution. His immune system will continue to make antibodies against his heart and will continue to need to use immune/anti-body suppressants meds...for his (pig's) heart. I agree with others who said that the pig must have been royally taken care of (for giving his heart/life) and that all future pig animals receive excellent treatment/life - before (that their heart be taken); there is too much a 'abattoir' vibe with certain animals - pig, namely (cows, beef..), - going straight to the slaughterhouse, now with 'organs ripped out' for other humans (at least, that is fair to the animal - we consume it entirely (sandwich meat (from pig)..and now organs (heart, from pig too); thus, it is more ethical...yes, pigs' population can be too high (pig overpopulation) and in that sense, eating them/using their organs 'curbs' their excess reproduction numbers in farms..(plus, we know that pigs are Very Very manure/poop producers, like cows and as such, need to be checked in numbers, or else, it will be a Gigamanure problem).
The problem (is) still, with this man, and his new animal heart...immune system rejection and now that he must take strong immune suppressing meds, as you said, his immune system will be weakened/partial % of protection...that's a serious long-term problem.
He may develop heart bacterial disease (due to pig heart), as the immune system's anti-body production around the heart is suppressed; later, the heart could succomb to bacterial/virus/microbial problem...because immune system (anti-bodies production/blocked) gone for the heart.
On top of the fact that it may be a Young Pig's Heart...(most likely, because, the organ will last the longest; vs an older pig's heart; but, I think the pig's need a least Some Time/Life before extirping their heart otherwise, it's basically extracting the heart from the Very Youngest pig...that means no life for the pig...now, we are not going to go into deep ethical debate...but, taking a heart, from a very yougn animal, means the animal had no life...but, a younger heart, as much chance of during much longer, for being biologically younger (per the epiclock, DNA dmage and ECM/morphology));
The way I see it, I thin his heart will tough 5-10 years, but above that, I have reservations; because pig's do not live a long life like a human; -their hearts, fail before that. Pig life is about 20-25 years....not much much more. Albeit, a well-fed (but not 'infinite fed'/control-fed) and laboratory protected pig, could last to 30-40 years; meaning its biological age would be slowed down considerably; and its diet changed too (thus, its size too/meat size too; this would affect its heart); if a pig's heart can last 20-40 years; 30 years avg...in the best light/at the best; then in humans, a young pig's heart, could yield up to half of that (I doubt it would translate 1:1...because a human body is different than a pig's body; a human has a different vasculature - this put a strain on the pig heart (transplanted in a human); the pig heart - is made/evolved for a pig (in size/shape); not a human. But, it works; I think that a Gorilla or Chimpanzee'S heart would be a substantially closer/better fit (for being related)...but, of course, this would open a can of ethics (they live long lifespans like humans as such we can't); we don't use primates hearts...pigs are ok, like cows, goats...all being meat at the supermarket.
5-15 years (10 avg) sounds about right for his heart. I hope it lasts much longer; it's scary though, he will need another transplant later, again (obviously); I hope nothing happens in terms of caching a deadly viral/bacterial disease (or even COVID/Omicron/or cancer.....etc) because immuno compromised by suppressing antiobodies production..immune system is crucial for longevity; you can't eternally suppress it. I guess we will ahve to find a (circumventing) solution
to this immune problem of organ rejection and needing to block antibodies formation (to avoid said rejection). We see it, in centenarians, old people...they often die of immune disease, viral, bacterial disease (pneumonia, tuberculosis...etc)...because, no more immunity - immunosenescence. Suppressing the immune system (via meds) will weaken it and can cause 'door open' (to die of) whatever viral/Bacterial disease...of that late age..
Just a 2 cents.
PS: It's still an incredible achievement...what's scary though is this ultra-invasive operation (changing an organ)...it's a pure luck of the draw (or draw of luck or unluck); if this operation fails...organ rejected totally...you die on the table. Thus, your life is in their hands - 100%. But, if your heart is failing..you are sure to die. You need a new heart.
But, you take your chances, and hope the operation goes correctly and the heart fonctions; or else, you don'T wake up (you die on the table). But, that's a risk, most would take, because if your heart fails...you are 100% sure of dying; so a new heart could be the only last solution, and yes, has a risk that you may die in the process 'of transplanting it' in you. But it's less assured, than not taking it and dying it from keeping your failing heart. I can wait to see this develop, with more biorganoids, and like other types of organs; as you said, only the brain we can't change...we'll have to figure it out/how to make brain and transfer data.../neuronal 'soul/identity/life/memories/recollection'...if it's ever possible. We often said it is impossible, but then, we were showed wrong, it was possible (just very very unlikely, but not necessarily, impossible, forever). For us, younger people (in 30-40s...) it' great news..but, it's tstill very preliminary and some people will refuse to do this, prefer to die than get transplanted...I'm sure of it.
PPS: This is where a synthetic 'Bioorganoid' - not animal organ..could be the solution...
either an electronic, mechanical or bioorganoid heart..coud circumvent the need to suppress immune system when transplanted an 'animal organ' in human (that gets rejected).
These other synthetic/artificial heart organ, could also be rejected..but it may be much less severe than the 'animal organ transplant' immune response/rejection. You still need some suppression (the immune system recognizes the artificial heart as 'foreign/invader') but maybe not as dire immune rejection - as like a 'live animal organ heart' transplant.
@CANanonymity
Yes to me the biggest issue is the immuno suppressant drugs. While what we have is a real technological miracle, we need a few other ones to make the pig or 3d printed organ 100% immuno-compatible. I am less concerned with ethics of harvesting pigs hearts. We eat them (well, i am vegetarian but for health and not ethical considerations , but I don't have objections my friends having a pork chops , as long as the total red meat consumption is moderate). And for sure a highly prized animal, which is a fancy bio-reactor will be taken much better care of than in a pig farm. We have domesticated pigs. But pigs have domesticated us. Currently there are more than half a billion pigs in the world. Yes, each individual faces a grim fate. But the species is more successful than ever. Some authors call this a deal with the devil. But nevertheless there more pigs now than there were humans just a thousand years ago. They fare much better than say lions or elephants who are on brink on extinction. In a way, if we switch to lab grown meat and organs, we will simply have to kill all the surplus pigs and reduce their population to a less than a million novelty pets.
As for the life expectancy prospects...
Today with human heart transplant the median survival time is about 12 years. Often it is 15. Actually not that bad. We don't know how pig organs will behave long term. In a way it is a big gamble but for the person there was little to lose. The patient is said to be on "heart support". I am not sure what that means but it sounds to be wired to a big-ass machine that probably adds oxygen and pumps your blood. Good that it exists but extremely expensive and sounds like it is prone to infections and complications.
And with heart transplants we have a few percent of recipients who don't even survive a whole year.
When (not if) the replacement hearts become more available (either 3d printed or chimeric animals) the heart transplant operations will become more routine , main stream and more efficient. It might take good 15 years to be mastered on mass scale but after that there will be robots surgeons doing 90% of the routine manipulations. It might be the new heap replacement.
This is predicated on good incompatibility , though.
For now we can joke about Richard "Pigheart" ...
Surely the approach being taken by Lygenesis would negate the taking immunosuppressant drugs problem.
https://www.nytimes.com/2022/03/09/health/heart-transplant-pig-bennett.html
Patient in Groundbreaking Heart Transplant Dies
David Bennett Sr. had received a heart from a genetically modified pig, a procedure that may yet offer hope to millions of Americans needing transplants.
The question is whether he died due to rejection or some other complication that would be there even with a well matching human heart.