Human-pig chimera (courtesy National Geographic)

Human-pig chimera (courtesy National Geographic)

WASHINGTON – Pushing the boundaries of medical ethics, scientists announced last week they have created the first successful human-animal hybrids, introducing human cells into a pig in a bid to harvest transplantable organs for humans.

Spurred by the fact that every 10 minutes a person is added to the national waiting list for organ transplants, while, every day, 22 people die on those lists because of a shortage of transplantable organs, University of Maryland’s School of Medicine is attempting to overcome the high probability of rejection through its creation of chimeras, an organism that contains cells and DNA of two different species – in this case, human and pig combinations.

Such experiments are currently ineligible for public funding in the United States.

But for lead study author Jun Wu of the Salk Institute, told the National Geographic that scientists only need only look to mythical chimeras for a different perspective.

“In ancient civilizations, chimeras were associated with God,” he says, and our ancestors thought “the chimeric form can guard humans.” In a sense, he says, that’s what the team hopes human-animal hybrids will one day do.

There are two ways to make a chimera. The first is to introduce the organs of one animal into another – a risky proposition, because the host’s immune system will likely cause the organ to be rejected. The other method is to begin at the embryonic level, introducing one animal’s cells into the embryo of another and letting them grow together into a hybrid.

At first, Juan Carlos Izpisua Belmonte, a professor in the Salk Institute’s Gene Expression Laboratory, thought the concept of using a host embryo to grow organs seemed straightforward enough. However, it took Belmonte and more than 40 collaborators four years to figure out how to make a human-animal chimera.

To do so, the team piggybacked off prior chimera research conducted on mice and rats.

Other scientists had already figured out how to grow the pancreatic tissue of a rat inside a mouse. Last Wednesday, the team announced that mouse pancreases grown inside rats successfully treated diabetes when parts of the healthy organs were transplanted into diseased mice.

The Salk-led group took the concept one step further, using the genome editing tool called CRISPR to hack into mouse blastocysts – the precursors of embryos. There, they deleted genes that mice need to grow certain organs. When they introduced rat stem cells capable of producing those organs, those cells flourished.

The mice that resulted managed to live into adulthood. Some even grew gall bladders, which are not normally seen in mice.

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The team then took stem cells from rats and injected them into pig blastocysts. This version failed. But pigs, they reasoned, have more similarities to humans.

When certain right human cells were injected into the pig embryos, the embryos survived. Then they were put into adult pigs, which carried the embryos for between three and four weeks before they were removed and analyzed.

In all, the team created 186 later-stage chimeric embryos that survived, says Wu, and “we estimate [each had] about one in 100,000 human cells.”

That’s a low percentage – and it could present a problem for the method in the long run, says Ke Cheng, a stem cell expert at the University of North Carolina at Chapel Hill and North Carolina State University.

The human tissue appears to slow the growth of the embryo, notes Cheng, and organs grown from such embryos as they develop now would likely be rejected by humans, since they would contain so much pig tissue.

The next big step, says Cheng, is to figure out whether it’s possible to increase the number of human cells the embryos can tolerate. The current method is a start, but it still isn’t clear if that hurdle can be overcome.

Even at this early stage, Cheng calls the work a breakthrough: “There are other steps to take,” he concedes. “But it’s intriguing. Very intriguing.”

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