You might not think that you should be excited about pig hearts being stitched into baboon circulatory systems, but boy are you wrong. Scientists have announced a new record for the survival of these Frankenhearts, and their work could have major implications for human health.
Every day, an average of 22 people die in the United States waiting for organ transplants. One possible solution? Get donor organs from other species. But that's not as easy as taking a trip to your local pig farm: Humans and pigs have enough anatomical similarity that we could, in theory, use their hearts to replace our own, but the human body would immediately reject the foreign organ. Doctors have a hard enough time getting human immune systems to accept organs from other humans, so you can imagine what a body might do if one from a pig suddenly showed up. To be fair, your immune system would be pretty lousy if it didn't react violently to the sudden presence of a pig heart in your chest.
To get around that, scientists are using genetic engineering to create pig organs that come just a hair closer to human-like – then testing them in baboons. But these baboons aren't having their own hearts swapped out. We're not at the point where scientists can trouble themselves over the functionality of these organs. There's no point worrying about that until they've figured out how to prevent the new host from rejecting the heart outright. So to see how well the host body can handle the pig heart without worrying about the heart's ability to, you know, be a heart, researchers just stitch the hearts into the abdomen, connecting them to the baboons' circulatory systems while leaving their own hearts to beat as usual.
In 2014, researchers led by Muhammad M. Mohiuddin of the National Heart, Lung and Blood Institute (NHLBI) in Bethesda, Md., announced that hearts from pigs with the human thrombomodulin gene added to their genomes had survived in baboon hosts for an average of 200 days, with some pushing past a year. They'd made several different genetic tweaks to pigs to test their relative success, but the thrombomodulin piglets produced the best hearts for the job by far.
Now they've beaten that record. In a study published Tuesday in Nature Communications, Mohiuddin and his colleagues report a median survival of 298 days. One graft host survived for 945 days.
This time around, the researchers focused on creating drug cocktails that would allow their hosts to sustain these transgenic organs. One solution is to just totally kill the host's immune system, but that's obviously not ideal, as it leaves one prone to all sorts of infections. Instead, Mohiuddin and the other researchers tried to create more targeted therapies. A surface protein called CD40 is vital for the communication between certain immune cells, so they used an anti-CD40 antibody to block it off. They also gave the baboons blood thinners, because clotting is a common immune response to the pig hearts.
Science magazine reports that four of the five baboon hosts (one died of an infection) were doing well until the researchers tried to wean them off the drugs. They all started to reject their organs, but the two baboons that had been on the immunotherapy the longest seemed to do quite well when tapered down to a lower dose of the drugs. But even those subjects rejected their organs once the drugs were cut off entirely, so the researchers removed the pig organs to save the four hosts.
"These hearts could have gone even longer, but we wanted to test to see if the animals had developed some kind of tolerance to the organs," Mohiuddin told the Verge.
Spending your life on an immune-suppressing drug cocktail isn't great, but it's a choice that many organ recipients must make. Still, there's a lot of work to do: Mohiuddin and his team have yet to replace a baboon heart with one of these transgenic organs. For now, all they have done is show that they can keep pig hearts from killing baboons. Now, they'll need to show that those hearts can actually keep the baboons alive.