Can pigs really be used as organ banks for human beings?

In the 1960s, researchers tried transplanting kidneys from chimpanzees to human beings. That effort seems amazing for at least three reasons. First, identifying a suitable candidate for a compatible kidney transplant often means that even close relatives are judged not compatible for a successful transplant. Second, chimpanzees are an endangered species, so it’s not as if a successful Pan troglodytes to Homo sapiens transplant route would have genuinely addressed shortages of human organs. Third, and perhaps most amazing, is that they had some success with this effort. Or at least, success in the form that some transplant recipients lived for months.

Over 110,000 patients are waiting for organ transplants in the United States alone. So the idea of an alternative source for these organs, one that doesn’t depend on either a steady stream of humans who are both compatible and willing to undergo a tremendous personal sacrifice, or compatible humans who conveniently die in conditions that leave them with a healthy heart, or lungs, or liver, has long been attractive. Watching a patient linger, sicken, and die while waiting for a compatible organ is a horror not just for patients, but for doctors, and it’s one they see over and over again. 

Writing this week in Science Immunology Megan Sykes and David Sachs of Columbia University Medical Center look at the state of long-running efforts to develop transplants from an animal that may at first not seem like the best possible candidate — Sus domesticus, the domesticated pig.

Pigs have actually been valuable in human health care for a long time. Even though the last common ancestor of pigs and people probably lived about 80 million years ago, pig skin is enough like human skin, pig hearts are enough like human hearts, and several other pig organs enough like human organs that they’re often used medical education and pre-clinical trials. Pig heart valves have been used in human transplants for decades. Also … there are literally a billion of them. Domestic pigs are, thanks to people who already like to transplant parts of pigs directly into their digestive system, the second or third most common large animal on the planet. 

Pigs are common, and pig organs are about the right size and right configuration, to replace their human counterparts. Pigs can also be bred in great numbers. Which brings the problem of transplanting them into humans down to the very serious issue of compatibility and rejection. But that’s a serous problem.

Most transplants, even transplants between highly compatible people, depend on immuno-suppression drug therapy to keep the immune system of the recipient from attacking the newly transplanted organs. Not only does immuno-suppression fail all too often, especially over a longer term, the use of these drugs often leaves transplant recipients open to infections because their immune systems have been intentionally weakened. For a “xenotransplant” — a transplant across species — to be successful, just using immuno-suppression drugs would mean cranking down the immune system to a level that would be unreasonable over any extended term.

But there’s an alternative. Recently, a number of experiments have demonstrated success in transplanting pig organs into non-human primates (and yes, that does mean still more chimpanzees in some cases). These organ recipients have survived months or years even with reduced levels of immuno-suppression. That’s not just because drugs have become better and more targeted (though they have) but because researchers have gotten better at designing pigs.

In particular, always in the news genetic editing breakthrough CRISPR and its more recent follow-ups, mean that pigs can be genetically modified so that there is less chance of their triggering an immune response leading to rejection. That includes techniques like “mixed hematopoietic chimerism” in which genetic information from the recipient is inserted into the donor animal. Put together genetic modification and improved drug therapy, and it seems like a billion new organ donors are just that far away.

And the conclusions of this review of current techniques show that “many of the obstacles that have previously inhibited progress in xenotransplantation have now been overcome.” That’s particularly true by using genetically edited pigs which make their organs more compatible with humans. Only  it’s not clear that we’re currently at the point where such transplants could be done without requiring large amounts of immuno-suppression. To get to an acceptable level for widespread use is going to require still more genetic tinkering with pigs … and maybe some genetic tinkering with people who are receiving organs from pigs. 

All of that may seem scary and, when the most difficult diseases to handle are already often those that make the leap from domesticated species, it may seem … a bit risky to more than just the people getting transplants. After all, bacteria and viruses already make the inter-species jump without someone building them a ladder.

But there are still those hundreds of thousands of people who are dying right now because there is no available transplant organ. And all those thousands of doctors who are watching them die. The incentives to make this work are extremely high.

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