Seventeen people in the US die every day waiting for an organ transplant, usually a kidney.

You would think that at  the rate of two per person, we’d have enough of those to go  around, but clearly we don’t. Scientists would love to create  their own kidneys using animals, to close the gap with human organ donors.

Which is why it caught our  attention when we read about a group that’s trying to  grow human kidneys in pigs. There are serious challenges to this  approach… technical, and ethical. But here’s how it might work. [♪ INTRO] The amount of donated kidneys that we have, and the amount that we would like  to have, are very different numbers.

Not everyone signs up to be an organ donor. Maybe they believe the scary myth that doctors won’t work as hard to save their lives. Just fyi, it’s totally different people  making that decision, not your trauma team.

Or maybe people just don’t know  you can sign up to donate a kidney or a bit of your liver while still alive. Cheeky link in the description if that’s  something you maybe wanna sign up for. There can also be logistical  barriers to getting donated organs to the people who need them in time, but  that is outside the scope of this video.

And there are other issues. Even if someone’s an organ donor,  they might not die in a way that allows procuring of their organs. And not all of us can part with a  kidney voluntarily, though again, if you wanna be a hero, that is a thing.

This is where the pigs come in. A team of researchers created and  grew combination pig and human kidneys in pig embryos using stem cells  from human umbilical cord blood, and published their results in the journal  Cell Stem Cell in September of 2023. It is a first-of-its-kind feat.

And if that didn’t seem weird  enough, other researchers are taking an opposite approach: making  pig kidneys just human enough. Research on xenotransplantation,  or transplanting organs and tissues from non-human animal sources into humans, has been advancing over the past decade. Scientists had already grown  human cells in other animals, including rats and mice, and humanoid  tissues like cartilage in pigs.

But this research represents  the closest we’ve come so far to growing solid, humanized organs in pigs. If it works in the long run, it brings  us closer to what some scientists call a holy grail for regenerative medicine. Most of us probably associate pigs with  summer barbeques or Stardew Valley.

And even though there are reasons they’re our model of choice for this kind of  research, it’s still pretty tricky. Non-human primates would  work a lot better than pigs, since they’re genetically similar to us. But for both legal and ethical reasons, we’re moving away from  using primates for research.

So we have to move on to other options. Pigs are relatively similar in size to humans, and their organs are set up in similar ways. Also, we know how to raise  a lot of them at this point.

Yes, even outside of farm games. But it’s not that simple. It’s not just size and anatomy that matter.

Research suggests that, the more closely  genetically related two species are, the better their cells will be able to  grow side by side without rejection. Humans are more genetically  similar to mice than pigs, and experiments have suggested that pig and human cells just don’t like to play nice. Part of the reason for that is  that pig embryos develop faster than human embryos, so they’re  developmentally out of sync with each other.

But a research team is working  on tackling each of those issues, in order to use pigs to grow human organs. In that 2023 paper, the researchers  engineered a chimeric human-pig kidney with human cells that could basically  outcompete the pig cells as the organ grows. Chimerism refers to any time you’ve got  cells with different genomes going on.

And it basically worked. For a while, that is; for  ethical and procedural reasons, they planned to terminate their  experiments early in fetal development. The key was using induced pluripotent  stem cells, also known as iPSCs. iPSCs are, first of all, stem cells.

These are the key types of cells that allow the development of an organism to happen. They have the potential to  become nearly any kind of cell, whether you need to make a  brain or a heart or a kidney. The induced part means the researchers  made these cells from other, more mature cell types, sending them back to cellular babyhood to make whatever they needed.

But that’s only the first part. To get the stem cells to make kidneys, the researchers had to  create a suitable host niche. This is basically the specialized  environment in the living body where stem cells reside and wait to differentiate  depending on the need of the day.

These niches naturally exist  in both embryonic development and in certain sites in adult connective tissues. The team had to give their human  stem cells a couple of legs up to be able to grow where pig cells would normally. They grew the cells in a specialized solution that helps keep them stem-y instead of  differentiating into mature tissue.

They also ramped up two genes associated with cellular survival to keep them kicking. Now, in molecular biology, what’s good for the goose isn’t always good for the gander. These genes are involved in  processes that tell cells to grow and keep them from dying.

In embryonic development, you want that. But those exact same processes  are also involved in cancer, so these are genes you want  to use very, very carefully. But at any rate, this means  the researchers had their human stem cells ready to make kidneys  in a place they normally wouldn’t.

Then they basically took pig  embryos, tweaked the pig cells to skip kidney formation, added  these extra-rugged human stem cells, and implanted their embryos in sows. About a month later, the sows were  pregnant with pig embryos with… well, not quite full kidneys, because kidney  development is wild in that they stop and start over, like, twice. But part-human, part-pig… part-kidneys.

The researchers collected  the embryos and found that the proto-kidneys were made  up of about half human cells. Some experts who weren’t involved  in the research have said that the proportion of humanized  cells is still too low. Also me, I am not an expert but  that seems like a low amount to me.

What’s more, only a very small  fraction of implanted embryos survived. Which means this approach is  nowhere near ready to go yet, from a purely scientific perspective. But researchers say it opens up an  exciting avenue for regenerative medicine, as well as an artificial means for  studying human kidney development.

Now, this is pretty wild. But there’s another research  group out there embracing the essence of “keep it simple, stupid.” Instead of a human kidney grown in  a pig, scientists working for the NYU Langone Transplant Institute  transplanted kidneys from genetically modified pigs into  two brain dead human patients. These researchers obtained explicit permission  from the families of the recipients, who had donated their bodies  to scientific research.

Most mammals that aren’t primates express a marker on their cells called alpha-gal. Since our cells never have the stuff,  our immune systems respond to it like a five-alarm fire, causing rejection of  animal tissue within minutes to hours. Sensitization to this same molecule  can cause a red meat allergy in humans, including those bitten by certain types  of ticks that carry it in their saliva.

The researchers basically  knocked out this single gene in the pig so that a human  host won’t reject its tissue. They also grafted a part of the pig's  thymus inside of the kidney ahead of time. This is a small gland in mammals and  certain other vertebrates involved in the production of T cells, a type of white  blood cell that fights off foreign invaders.

The thymus is also involved in the  destruction of T cells, and some research has shown that when a piece of  thymus is grafted to a donor kidney, it works to prevent the immune  system from attacking the organ. The alpha-gal knockout worked. In their most recent attempt at time of  writing, one of the kidneys functioned for 61 days without being rejected, at which point the researchers concluded the experiment.

The thymus graft may have also had  something to do with this success, or it might have just been the alpha-gal. The researchers aren’t totally sure. Which really begs the question of why you’d mess around with that other thing, right?

Knock out one gene and we’ve  got all the kidneys we need! Well, it probably isn’t that simple. Two months is great, but donated  organs usually last around a decade.

The thymus graft is supposed  to increase immune tolerance, but we’ll need to see that happen over  a long period of time to believe it. And there may be some advantages  to the iPSC-based approach. You can make iPSCs from a patient’s  own cells, which could mean we’d be able to sort of clone a kidney  for a person using a pig; a kidney that’s pretty much genetically  identical to their own cells.

And the researchers say it’s also a  way to study the development of human kidneys, even when the approach isn’t  being used to produce donor organs. So yeah, we’ve established that you can  probably grow humanoid organs in pig embryos, and that genetically engineered  pig organs can function in human bodies. But we would be remiss to gloss over  the age-old sentiment made famous by old stories like  Frankenstein and Jurassic

Park: without really, really robust safeguards,  what if things get out of hand? Some parties argue that research into  induced chimerism and xenotransplantation is unethical in certain circumstances, while others say it’s inherently  unethical regardless of the consequences. Their reasoning is based on unease  about mixing human and animal tissue. What human characteristics might they acquire?

Could they reproduce? Would  they be smart, like us? These concerns aren’t necessarily likely,  and a pig grown for its human-based kidneys is not going to stand  up and start reciting Hamlet.

But it’s still something  researchers should account for. And the authors of the chimeric kidney  study noted that they found a couple of human cells in the pig embryo brains. Only a couple, but that’s still  a part-human brain if you squint.

They think they can fix this by  knocking out genes in the human cells, but worry it could cause  problems in the growing kidney. Another major ethical concern is that  animals’ rights would be in question in a way that’s distinct from killing them for meat, which is its own huge can of worms. And this goes for any approach where we’re using organs grown in nonhuman animals.

See, doctors have a responsibility to  protect patients from the risk of zoonotic, or animal-transmitted, disease. Patients have a right to receive an organ that won’t make them sicker  instead of making them better. In particular, there’s this sort of  fossilized virus that lives in pig DNA, called Porcine Endogenous  Retrovirus or PERV (yes, really) that could hypothetically wake  up and cause problems on purpose.

That means keeping pigs under very  different conditions than what you’d see on a farm: restraining them,  monitoring them frequently, and keeping them isolated. Like us, pigs are social animals. To protect patients’ rights and safety,  you’re creating what some scholars have called unacceptable circumstances  for raising those animals.

And one further wrinkle: for all medical research, you have to obtain informed  consent, meaning you have to tell patients what they can expect,  and they have a right to opt out. If you put an organ in someone, and then  you have to monitor that organ to see if any zoonotic diseases manifest, for  life, that person can’t opt out, can they? The researchers who performed the  alpha-gal transplants say that the risk of zoonotic disease  is probably really low because there have been no recorded cases  of PERV being transmitted to humans.

Further research and clinical  trials will elucidate these risks before any of  this happens on a large scale. Finally, while pigs have their  advantages and disadvantages, this research doesn’t do a lot to account for the worldwide prevalence of pork taboos. Sure, faith leaders and communities  might decide that saving a life is worth breaking that taboo, but by doing all this  in pigs, you’re asking them to do that.

So, both technical and ethical hurdles  still abound before pigs can be used as a major supply of organs  for human transplantation. But scientists don’t dispute that the  new developments are a major step toward getting humanity’s hands on the holy  grail of an unlimited organ supply. As always, remember that  this is an internet video.

We’re not on here to deliver a final answer on whether those pursuing this  grail should be doing so. But this research is absolutely fascinating,  even if it does seem pretty out there. One thing’s clear: progress in  this field could save human lives, and everyone agrees that’s a goal worth pursuing.

For now, organ donation’s  still the best that we can do, but I’m looking forward to  the day that that changes. I hope you learned a lot from today’s  video, because we worked really hard on it. But while we can offer you lots of knowledge, one thing we at SciShow cannot  give you is college credit.

But with the Study Hall channel, you can start taking college  courses right here on YouTube! Here’s how it works: Watch the course videos on the  Study Hall channel for free, then sign up for an online  college course led by ASU faculty for just $25 and apply what you’ve learned. If at the end of the course  you’re happy with your grade, pay $400 and now you have 3 transferable  college credits on your transcript.

That’s about a third of the  cost of a college course! Like the Code and Programming  course that teaches beginners with no coding experience how to develop JAVA programs. Throughout the course,  you’ll write simple code that gets the computer to do complex  tasks like data management.

Or if you’re looking for other  common gen-ed college courses like Modern World History and Human Communication you can find them on the Study Hall channel too! Whether you’re trying to learn  new skills, earn college credit, or just prove to yourself that you can do it, Study Hall can help you reach your  goals without the financial risk!   Check out the link in the description  or go to GoStudyHall.com to learn more. [♪ OUTRO]