Hank Green: Organ transplant waiting lists  are a race against the clock. Patients on kidney transplant waitlists have to hold out an average of more than three years. On top of this, organ transplants  need the immune system’s seal of approval to be accepted by the body, and the immune system is extremely picky. But for patients who need a kidney ASAP, scientists might have found a way to safely circumvent the body’s overzealous security system.

And it’s by changing their blood type. Yeah, kidneys have blood types. Here’s how and why this might work.

[0:34] [♪INTRO]

[0:37] Hank: In 2019, 40% of end-stage kidney disease patients died within three years of starting dialysis… and only 11% could be added to transplant waitlists. Finding enough donor organs is complicated, and supply and demand isn’t the only problem. Doctors need to consider the possibility of the immune system rejecting a transplant. The immune system is like the body’s bouncers.

At its core is a type of cell called a B cell, which generates antibodies. These are highly specialized proteins that can attach to markers called antigens on the surface of invading cells. This helps the body distinguish “non-self” from “self”, and take out, say, a cold virus as soon as it makes its way into your nose.

Once the antibodies grab onto an invader, they can call in backup, including other immune cells, to take care of the intruder. This system works across all types of new biological material that enters the body: viruses, bacteria, parasites and even blood. Now, you might be used to thinking of other antigens responsible for organ rejection.

Like the major histocompatibility complex, or MHC, markers that make it incredibly hard  to match donors with recipients. But our organs also express blood group antigens on their cells – the A, B, and O you’re probably familiar with. And if you have blood group A, you can’t get a kidney from someone with blood group B any more than you can get their blood!

Blood types are dictated by sugar chains on the surfaces of our cells, both blood and tissue. Cells can express sugar chains dubbed A or B. They can also express both chains, making them type AB, or neither chain, making them type O.

The type of antigen is dictated  by genetics, and people generally have antibodies against the types their cells don’t express. But there’s one way to not be recognized by those antibodies, and it’s to not have any A or B sugar chains – that is, to be type O. This is one way scientists have tried getting around the limitation of not having a fully compatible transplant organ.

By removing the cells’ blood group antigens, scientists can basically make everything type O. And this has some extra perks: first, type O is the most common blood type. And the demand for type O donor organs is high across all blood groups, not just O.

That’s why type O is considered  the “universal donor”, since O blood cells can go to any other blood type. Second, type O also has  the pickiest immune system, treating both A and B antigens as invaders. So disguising as type O, which lacks both antigens, lets the organ go stealth mode, unnoticed by pretty much everyone.

This also gets around some of the issues involved in immunosuppression. Doctors can suppress the immune system for major procedures, telling the immune cells to take  a nap while the body is healing. This can lower the risk of transplant rejection.

But along with the benefit of  limiting the patient’s antibodies against transplanted cells, this has the cost of limiting the immune system’s ability to recognize real threats, too. If, instead of suppressing the  immune system, we could disguise the transplant cells that we’ve  already vetted, patients could have the benefits of a transplant  without sacrificing immunity. And that may be possible, but before we talk about that, let’s go to a quick ad break.

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It’s a year of curiosity, delivered in one box. You’ll get 40% off the first box with code sci40 and also a free Denary Dice to all new subscribers. In a paper published in 2025, scientists were able to use this principle to modify the blood type of kidneys for transplant.

The transplant was done on a  brain-dead patient with consent from their family, using blood type A kidneys with a type O recipient. In this case, the doctors used a specific enzyme to pop off the type A antigen on the kidney cells before doing the transplant, making the transplanted organs basically type O… for a while. For about 2 days, that is.

Since the kidneys’ cells still had the genes to make type A antigens, they started  replacing them fairly quickly. But even though the transplant  was ultimately rejected, this was a step in the right direction. Now that we know the transplant process can work, if scientists can extend the time  that a transplant goes undetected for just a couple weeks, the  chances of success increase greatly.

That’s because sometimes, even incompatible transplants can reach a sort of truce with the recipient’s immune system in a process called accommodation. Even if the organ is under attack from antibodies, it may be resilient enough  to resist failing completely. If the organ is still standing after a few weeks, chances of rejection are way lower.

As this research progresses, disguising a transplant organ’s blood type as O could expand the donor pool. You’d still have to deal with other mismatches, but blood groups could become a non-issue. Scientists have also used cells and tissues from non-human animals, modified to be compatible with humans, in transplants.

This idea, called xenografting or xenotransplanting, is surprisingly old, with recorded xenograft attempts as far back as the 1800s. But things have improved a lot since then. Another 2025 study claimed to sustain a gene-edited pig kidney in a brain-dead human  patient for two full months.

Xenotransplants like this could make the donor pool even bigger to meet patient demand. This is especially true with growing knowledge of what edits to genes and antigens we need to make, and new ways to make them. In medical research, the path from proof of concept to practice is a long road full of replication, confirmation, and safety checks.

As it should be, when there are lives on the line. But even if it’s still early, transplant  work with kidneys is promising, and this principle can be applied to other organs, too. Blood type-incompatible transplants and related studies are being done with liver and lung tissue, among others, though each comes with its own unique challenges.

But this is a pretty amazing, and surprisingly simple, way to expand access to transplants. Really drives home the idea of the “universal donor.”

[7:09] [♪OUTRO]