New, controversial animal hybrid research may one day save lives

New, controversial animal hybrid research may one day save lives
February 8, 2017

It's not news of a flying car, a laser gun or a jetpack, but two major studies of a different subject published this week that seem to have walked off the page of a science fiction novel. Scientists have created hybrid animals: one animal containing cells and organs from another.

These hybrids, named chimeras in the scientific community after the mythical creatures with the heads of a lion and a ram, could provide medical benefits to millions of people around the world, but not without raising some serious ethical questions on the way.

Mythical ChimeraThe mythical chimera had the power to breathe fire. The chimera that researchers are working toward would have the power to grow human organs: kidneys, livers, lungs and hearts ready-made for people who need organ transplants. With more than 70,000 Americans currently waiting for organ transplants, this power could save thousands of lives every year.

A chimera capable of providing whole, functioning organs still sits in the realm of science fiction, but the two new studies represent tangible progress toward making them science fact.

In the first, Japanese scientists created mice with the pancreatic tissue of rats. The mouse embryos were genetically altered so that they could not develop a full pancreas, and then injected with pluripotent stem cells—the ones that can transform into anything—from rats. These rat-mice grew up to have fully functional pancreases with rat versions of the specific parts that make insulin.

What makes this study, published in the journal Nature, stand out is that the researchers were able to successfully transplant pancreatic tissue into diabetic mice. Not only did the diabetic mice take the rat-mouse tissue without rejection, but also their diabetes was kept under control for more than a year after the transplant.

Mouse-rat and rat-mouse chimeras have both been made before, but the success in treating diabetes with chimeric tissue is groundbreaking.

The other study, which came from the Salk Institute in California, aimed to improve the effectiveness of using stem cells to create multi-organ chimeras. They used a gene editing technique called CRISPR-Cas 9 to comb through animal DNA at the earliest stage of development and cut out some of the segments that contribute to creating internal organs. Then when the embryos had grown larger, they injected pluripotent stem cells from other animals, including humans, to see to what degree the organs came out looking like those of a different species.

Chimerized Mouse

They made their own rat-mice using this method, and the resulting chimeras had functioning mouse organs with rat cells integrated. The most effective transformation was in the heart, where roughly 10 percent of the cells were rat, but rat cells were also found in the brain, lungs, liver, pancreas and kidneys. Beyond that, the researchers report that many of the mouse-rats lived to adulthood and one even lived to the age of two, a long life for a mouse. This demonstrates that chimeras can viably live into adulthood.

They also attempted to use similar methods to create animal embryos that could host human cells. Scientists have had great success creating mice with human immune systems for research, but creating whole organs has proven to be much more challenging than getting mice to produce the free-floating cells of the immune system.

The researchers injected pluripotent stem cells at three stages of their development—completely undifferentiated, primed into the action of differentiation, and a phase in between—into the embryos of cows and pigs. Cows and pigs would be the ideal species for human chimeras because they are large enough to hold human organs. Pigs have the edge between the two because they are so similar in size to humans and their bodies are similar enough to ours that human organs could more easily power a pig.

The human stem cells were not always a success in creating functional embryos. In some trials about half of the embryos had stunted growth. The undifferentiated and intermediate stem cells, however, did successfully implant into the embryos of both pigs and cows. These are the first cases in research of any sort of chimeric hybrid between humans and large animals.

There are a few caveats here, however. First, these human-pig hybrids were not allowed to grow beyond four weeks, so the long-term viability of these hybrids is unknown. Second, even if these chimeras grew to maturity, they would not be anything close to a 50-50 man-pig. The researchers say the percentage of human cells in the pig embryos were orders of magnitude smaller than that of rat cells in the rat-mice.

Still, the importance of any human cells taking hold in the pigs cannot be overstated. According to the U. S. Department of Health and Human Services, 22 people die every day while waiting for an organ transplant. And though humanized animal chimeras have literally not even reached their infancy, a future where we could grow human organs in animals to save those lives has taken a major step towards conceivable reality.

Mouse EmbryoWith impending reality, however, comes the impending need to address the ethics of conducting this type of research no matter how far down the away that reality is.

There are a number of potentially questionable facets of this type of research including animal welfare, the potential blending of different species and the humanization of animals. The National Institutes of Health currently has a moratorium on funding chimera research until these types of questions are answered.

Each topic is tough to tackle. Harvesting organs for transplant, one could argue, is not that much different from raising livestock for meat or using animals to create vaccines. The issue gets stickier when you consider how having human organs affects these animals’ quality of life. The organs should perform essentially the same functions, but they are not identical. As humanized chimeras have never progressed beyond embryos, we have no idea whether having slightly different organs is painful. We have no way to know, but just as consumers and regulators demand higher standards for livestock, so we would demand them for chimeras.

The ethics get stickier still when you consider that on a cellular level, the chimeras are part human. While indeed, having human organs to transplant is the entire point, the rat-mice in the second study showed rat cells growing in the mouse brains. If the same thing were to happen in humanized chimeras, then in theory researchers would be able to create animals capable of some degree of human intelligence.

Previous studies have shown that mice with human support cells in their brains have roughly four times the memory capacity as normal mice. As of now, there have not been any full replacements of animal brains with human tissue, but horror movies like the new Planet of the Apes franchise and Deep Blue Sea have been built around the idea of animals with human intelligence, an idea that captures the fears and imaginations of many. Current research aims to keep human cells out of chimeric animal brains.

Each issue is difficult to tackle, but they need to be addressed in order to ensure the ethical treatment of any chimera subjects and to assuage any fears that researchers are creating The Fly. With tens of thousands of lives to be saved, responsible chimera research could make a fundamental difference in fulfilling the need for transplant organs.

—Daniel Lane

Daniel Lane covers science, medicine, engineering and the environment in North Carolina.

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