Human-Pig Chimera Embryos Have Been Created

The injection of human pluripotent stem cells into a pig blastocyst. The red cross represents where a laser perforated the blastocyst outer membrane so the cell can be added. Juan Carlos Izpisua Belmonte

The world is a little closer to one of the ethical dilemmas we have put off thinking about. Embryos have been produced combining DNA from pigs and humans to make a so-called “chimera”. They were allowed to develop for weeks before being destroyed. Almost certainly, such chimeric embryos will soon go further, but technical challenges have made their formation harder than scientists expected.

Chimeras are organisms formed from two fertilized cells or zygotes, particularly those from different species. They sound like they should stay in the pages of J.K. Rowling books or ancient mythology, but there are good reasons why some want to create them. Most notably, people are dying from a shortage of donor organs such as hearts and kidneys. Chimeras, particularly those made by combining pig and human fertilized cells, could offer a solution, producing organs that are similar enough to our own to be transferred effectively.

The idea strikes many as horrendous, but others argue it is no worse than raising animals, often in shocking conditions, purely to eat them. It also might be hard to tell someone whose only hope of survival rests with a chimeric liver that the idea is too repulsive to implement. Science fiction writers and philosophers have spent some time wrestling with the issues, but political institutions and the wider public have generally put it in the basket of difficult things we don't have to worry about just yet.

So the announcement in Cell of the successful creation of a pig-human chimera embryo serves as a wake-up call that we can't put off thinking much longer about whether this is something we should do.

The efforts of lead investigator Professor Juan Carlos Izpisua Belmonte of the Salk Institute and his team have showed that the obstacles are not just ethical. “The ultimate goal is to grow functional and transplantable tissue and organs, but we are far away from that,” Belmonte said in a statement. “This is an important first step.”

Izpisua Belmonte started by putting rat stem cells into a mouse embryo, something others have previously achieved. He then used gene-editing tools to delete the mouse genes responsible for the development of specific organs and replaced them with the rat equivalents. "The rat cells have a functional copy of the missing mouse gene, so they can outcompete mouse cells in occupying the emptied developmental organ niches," said first author Dr Jun Wu, also of the Salk Institute.

Human stem cells have previously been introduced to mouse embryos, but results have been poor. Izpisua Belmonte and Wu went large, leading a team of 40 people in an attempt to introduce human cells into cows and pigs. The bovine portion of the work proved more difficult and expensive, and was dropped in favor of a focus on pigs.

Even this wasn't easy, however. Pigs take less than four months from conception to birth, so development is much faster than for humans. "It's as if the human cells were entering a freeway going faster than the normal freeway," said Izpisua Belmonte. "If you have different speeds, you will have accidents."

Although the team eventually managed to get intermediate human pluripotent stem cells to form a chimera within a porcine embryo, the product was more pig than man. The authors consider this a good thing, since many of the biggest ethical issues would arise with the creation of a creature with a human-like brain.

The embryos were destroyed after 3-4 weeks, having demonstrated their viability to that point. The authors are working on inserting specific human genes into subsequent chimeras (as was done with the rat-mouse predecessors) to make more human organs.

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