Of pigs and people


Calm down, people. Nobody is making human-pig hybrids, even if the news is making a big deal about it. To be honest, I’m not even very impressed with the utility of the experiment, although it is interesting and technically accomplished. It’s being touted as a step in developing pigs with human-derived organs for transplants, and no, I just don’t see it.

The experiments involve xenografts in the blastocyst; that is, they take pluripotent stem cells from one organism, and inject them into the embryos of a different species at a very early stage of development, when the embryo is a hollow ball of cells with an inner cell mass that will eventually become the fetus proper. Then they look for incorporation of the injected cells into the embryo.

It doesn’t always work. The inner cell mass doesn’t necessarily accept these alien cells, or the injected cells don’t thrive in this unusual environment, so you might do the injections, implant the resultant hybrids, and when you open up the host days or weeks later, your injected cells are all gone. It is non-trivial to get this to work, so what they’ve accomplished is technically impressive.

It was a lot of work, too. They injected 2,181 pig blastocysts with human pluripotent stem cells, cultured them in vitro for a few days, and had 2075 embryos that were then implanted in masses of 40-50 embryos into host pigs (which implies that many would be expected to be lost), and collected 186 embryos about 4 weeks later. This is a good yield — I’ve done experiments with much lower rates of success — but the real question is whether any of the human cells were incorporated into the pig embryos.

It worked! They got incorporation of human cells into the pig embryos. Unfortunately, there are a few problems: one is that the embryos with incorporated human cells were significantly retarded in their growth. This ought to be expected; just the timing of development for the two kinds of cells will be out of sync, so I’d actually have expected even greater problems. It’s promising that they got incorporation at all. The other problem is that the incorporation was very low: 0.001% of the embryo’s cells were human. Uh, that’s not very good. If you’re trying to generate organs grown in pigs that have exclusively human antigens, even 99.9% human isn’t going to be good enough — it’s going to trigger an immune response when transplanted.

None of these cells made up the majority of cells in any organ, even; the experiment doesn’t really test the feasibility of accomplishing that, and I suspect that trying to increase the percentage of human cells is going to also increase the incompatibilities and lead to greater and greater rates of developmental failure. They do have some interesting ideas for increasing the rates, though. If the host pig cells are transgenically modified to make them unable to make a pancreas, for instance, any pancreas in the pig would have to be derived from human cells. It would still be infiltrated with pig-derived nerves and blood vessels and connective tissue, though, so that’s insufficient to create a transplant-ready organ.

As pure basic research, it’s a good experiment, and I’ll be interested to see how much further it can go — if nothing else, it’s going to expose evolutionary disparities in development between different mammalian species. The head investigator has an appropriate perspective on it, I think:

Scientific American: So this is very, very basic biology?

JCIB: So I feel that there has been a little bit of exaggeration of where we could go with this now. If you look on the Internet you see images of chimeras between human and animal. And I feel that that’s a little bit of exaggeration. It’s true that it works very nicely between rat and mouse — just this experimental protocol that I am telling you. It’s only a couple of months ago that we have been able to put human cells into another animal. In this case in a mouse and realized that they can differentiate in the three germ layers. The three germ layers are the mesoderm, ectoderm and endoderm that will give rise to the more than 250 different cell types. So that’s a major accomplishment I will say. But from there, dreaming that they will generate a functional structure, I think we’re going to need time and a lot of luck.
So we need to go for a lot of basic research still. It’s my own feeling, of course. There are other people who think that tomorrow we are going to create human organs. And I wish that I am wrong and they are right, but I think it will take time.

Yes! It’s basic research, which is a grand and worthy thing. It’s too bad so much of the press coverage can only grasp it in terms of making organs for human transplantation — I doubt that this approach will ever work for that, but will instead teach us more about development and evolution and molecular biology.


  1. slatham says

    How did they determine the precise proportion of cells that were ‘human’? Just that seems like an incredible technological accomplishment. Is it credible? Did they sample individual cells or did they do PCR on a mass and compare amounts of human vs pig product? Or something else?

  2. says

    #1: ” To facilitate the identification of human cells in subsequent chimera experiments, we labeled hiPSCs with either green fluorescence protein (GFP) or hKO fluorescence markers.”

  3. marcoli says

    What has been going on for some time is to develop transgenic pigs with human histocompatibility antigens for xenotransplants. Hypothetically far more useful and sustainable. I don’t know how far that has come.

  4. Callinectes says

    I am not entirely opposed to human-pig hybrids.

    If I had the equipment and expertise I’d be attempting to create all kinds of horrors at home, free of any ethical oversight. For too long the world has been without a good old-fashioned mad scientist, a bio-engineering villain working in something more original than mere diseases. Someone hybridising creatures more or less at random, throwing piranha genes into everything for kicks until something weird is born that actually lives. Let those right-wing papers fear something that is actually real, for once. Let them know the true meaning of horror! Let parliament scrabble desperately to complete legislation even they do not understand! Let the zoos and aquariums and Jurassic Parks of the world suffer fantastic losses in revenue as my monsters occupy the world’s imagination! Let the sushi restaurant daily specials spiral wildly out of control! When genetic chaos reigns, my impossible creatures shall reign over humanity.

  5. latsot says

    The article I read about this ended with something like “but some people are worried about scientists putting human brains in pigs.” That was the actual last sentence in the article.

  6. zetopan says

    “I am not entirely opposed to human-pig hybrids.”

    Does this mean that you actually support the human-pig hybrids that moved into the White House?

  7. blf says

    …some people are worried about scientists putting human brains in pigs.

    Some people may be worrying about that, but most pigs are panicking…

  8. blf says

    Does this mean that you actually support the human-pig hybrids that moved into the White House?

    If there really are some which did so, then possibly — they have got to be better than the orange daleks !

  9. DLC says

    Oh sure. . . isn’t it obvious to anyone who can think that these scientists are creating Gamorrean guards ?
    The reptilian overlords commands will be obeyed !

  10. Rich Woods says

    @Callinectes #7:

    Excellent! Do you need a henchman? I’ll change my name to Igor, if it helps.

  11. Ichthyic says

    Nobody is making human-pig hybrids, even if…

    …Ken Ham is still busy raping piglets every day.

  12. Pierce R. Butler says

    … even 99.9% human isn’t going to be good enough — it’s going to trigger an immune response …

    Wouldn’t it make more sense (genetically if not ethically or practically) to focus such work on chimpanzees & bonobos, if you want to go the transgenic route?

    About 30 years ago, I saw a piece in the Wall Street Journal about pigs born with a shot of human DNA in an attempt at engineering low-fat pork. It didn’t work – most or all of the animals developed crippling arthritis – but has given me the creeps regarding what I call “industrial cannibalism” ever since.

    Meanwhile, of course, Cordwainer Smith had organ-farming all figured out in 1961:

    … he finds himself face to face with his fellow prisoners. There are people with extra limbs, noses, eyes, organs, and in one case a string of human torsos attached to them.