Human-Pig Chimeras: Questions, Concerns, How They Work

There was recently a cool study published in Cell about making human-pig chimeras that was exciting enough to make the news a few weeks ago. I’m not surprised, since the research is a move towards solving a big problem: organ donation shortages. The US Organ Procurement and Transplantation Network reports that 22 people die each day waiting for an organ transplant. Most healthy organs are being used by healthy people who also need them and/or are understandably unwilling to take the risk of donating a kidney.

The other reason I’m not surprised it made the news is that making human-pig chimeras is off-putting to a lot of folks. I think the idea of human-pig chimeras raises a lot of interesting and important ethical and theological  questions about how we understand who we are and our relation to other life.

How Can This Work?

Scientists have actually been making inter-species chimeras for decades now. It’s a classic developmental biology experiment using a technique that was pioneered by Nicole Marthe Le Douarin, and has let us learn a whole lot about how different organisms develop. In the classic experiment, the idea is pretty simple: you take two organisms that are similar and at similar early stages of development, you carefully slice off a particular piece of each, swap the pieces, and see how they grow.

Classic developmental biology experiment. Graft part of a quail embryo onto a chick embryo and see how it develops.

In the classic example, part of a quail embryo gets grafted onto a chick embryo. The reason is that quail cells are easy to distinguish from chick cells when you look at them under a microscope. The super cool and useful thing about this experiment is that you can then watch to see where those quail cells go. Many experiments have been done this way to do something called Fate Mapping, which is figuring out which cells end up where at different stages of development. This lets us know which parts of the relatively early embryo in the picture above will eventually form a brain, or wings. . .

A chick-quail chimera. Mostly chick, but with quail wings. Images from the Society for Developmental Biology

This is not exactly how human-pig chimeras were made, but it’s a similar idea. These experiments do give us needed information to make human-pig chimeras to grow donor organs: what cells turn into different organs, and where they have to be to turn into those organs. If you think about it, all the cells in a complex organism like a chicken are the offspring of a single cell. How do the cells end up so different? They respond to different signals that are in different places in the embryo during development. If you give some pluripotent stem cells the right signals at the right time, they can turn into any body tissue you want.

That’s the dream anyways. We’re not there yet.

So what’s the story with this new study?

The Wu et al. human-pig chimera experiment that recently made the news was actually pretty simple. They took some pluripotent (can become almost any cell type) human stem cells and put them into some pig embryos. Instead of using later stage embryos like in the graft picture above, these scientists mixed the cells at the blastocyst stage, which is a really early stage. Earlier means fewer cells around, and that means it’s harder to control where they will end up.

An example of injecting cells into a blastocyst. Note how few other cells there are. (Source)

The results reported in the paper were modest. They grew the embryos for a few weeks inside some sows and then checked to see if there were still human cells inside. There were, which is the big news. They have some pretty nice microscope pictures with the human cells labelled in the paper itself, so click over and have a look if you’re interested.

Just getting human and pig cells to grow side-by-side in an embryo is a new thing. The less exciting news is that it seems few human cells survived, and a lot more work needs to be done to get to figure out how to usefully grow human organs in pigs. A known problem with trying to do this is that the pig cells will out-compete the human cells to build the organs.

The hope is that someday we can genetically turn off the pig cells’ normal ability to make certain organs, and maybe use some of that fate mapping  to put human cells in the right place to make the organs instead. Science takes time and hard work. In the mean-time, the possibility of this future technology raises a lot of pretty interesting questions and concerns.

Some Concerns

For one, the thought of part-human-part-pig creatures tends to give folks a sort of general uneasy sort of grossed out feeling. It’s hard to say what to even think about such a thing, so it’s best to be careful. At least in the US, the NIH is not currently funding such research because of this, but the talk is that they’re working on changing that. The fact of the matter is, this research is so promising for growing needed human organs in the future that a general feeling of “I don’t know what to think about this” is not a strong enough reason to prevent the work from moving forward eventually.  We would need strong and clear reason to block such research altogether. We don’t have such a reason currently.

There are some hypothetical risks that give clear reasons to not just let these human-pig chimeras grow to maturity right now, though. As mentioned, it’s hard to say where the human cells would end up. What if there were a lot that ended up in the brain? The absolute worst case scenario would be an essentially human brain inside a pig’s body. What if they ended up in the gonads? Could two such pigs produce a human child? These outcomes seem pretty fantastical, and pretty unlikely. But the thing is, we just don’t know what would happen, but we do know some bad stuff could happen, so careful step-by-step experiment is definitely warranted.

Some Questions

I find the questions that this sort of work raises to be pretty fascinating. I think what makes some folks leery about this sort of thing in general is a perceived breakdown of the wall between human and animal life. This can be unnerving, since we’re pretty comfortable doing things like killing and eating animals, but not so much with humans (fortunately!). The fact of the matter is that a human-pig chimera would be part human cells and part pig cells. So how should we treat such a creature? Different than a normal pig even if it acts the same and looks the same?

When exactly does a creature classify as human? When it reaches more than 50% human cells? Picking an arbitrary percentage like that doesn’t seem like a rational way to figure out such a thing.

Part of the answer to those questions is a more theological question: what exactly does in mean to Christians that humans are “in the image of God”? For those who would ascribe some spiritual significance to human cells in general, any human-pig chimera is going to be morally insulting. On the opposite extreme, is the image of God just human faculties  and not the human form in any respect? If that’s the case, would we also be comfortable with something like growing genetically engineered brainless human bodies to harvest organs from? That sort of thing may be even further into science fiction territory, but is a reasonable possibility in the future.

For now, we can sort of enjoy the fact that these questions aren’t imminently bearing down on us. But the future is coming. This technology is being developed. It will be better to try to sort out reasonable answers soon before we need them. I’m hoping to explore some of these questions more specifically in some future posts.

Scientific Literature Cited

Wu, J., Platero-Luengo, A., Sakurai, M., Sugawara, A., Gil, M.A., Yamauchi, T., Suzuki, K.,
Bogliotti, Y.S., Cuello, C., Valencia, M.M., et al. (2017). Interspecies Chimerism with
Mammalian Pluripotent Stem Cells. Cell 168, 473–486.e15.

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