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March 4, 2018

Science of the Lambs: We can now grow human cells in sheep

by John_A

N-Sky/Getty Images

Strange creatures have emerged from Pablo Ross’s University of California, Davis lab. They’re neither strictly sheep nor fully human. Instead, they’re a bit of both.

In a biotech breakthrough — the second of its kind in just over a year — Ross announced at the American Association for the Advancement of Science last week that he and his colleagues have successfully grown nonhuman animal embryos that contain human cells. Previously, the host species were pigs. Now, they’re sheep.

They have the potential to revolutionize organ transplantation and help save thousands of lives.

These human-animal hybrids, or interspecies chimeras, are not just the product of bizarre experimentation done for the sake of science. They have the potential to revolutionize organ transplantation and help save thousands of lives each year in America and around the globe.

Though this breakthrough brings us one step closer to growing transplant organs inside host animals, it also comes with some ethical baggage. Bioethicists and animal advocates alike question whether human-animal hybrid studies are worth the potential cost of animal welfare or the risk of creating nonhuman animals with humanlike qualities.

Why chimeras?

There’s an organ shortage in America that sees approximately twenty people die while waiting for a transplant every day, according to the U.S. Department of Health and Human Services. Minus the roughly 16,000 suitable donors and 33,600 transplants in 2015, nearly patients 120,000 remained on the waiting list. In the simplest terms, there isn’t enough organ supply to satisfy demand.

A pig embryo injected with human stem cells that grew to be four weeks old.(Salk Institute)

“Organ transplantation has been extremely successful and saves a lot of lives,” Ross, a UC Davis animal scientist, told Digital Trends. “The problem is there are those that get the organs and those that don’t, because there are not enough organs for transplant.”

But, if scientists were able to grow human organs inside host animals, they could potentially generate enough organs to eliminate the shortage all together, saving thousands of lives annually in the U.S. alone.

Prior chimera studies, including one in which scientists grew a rat pancreas inside a mouse, give evidence for this approach. But human organs are much bigger than rats’, so Ross and his colleagues have had to focus on larger livestock.

“If we want to grow a human organ we’ll have to go to an animal larger than a mouse or a rat,” he said. “Pigs and sheep have some important characteristics that would make them a good host species for growing the human organ.”

“If we want to grow a human organ we’ll have to go to an animal larger than a mouse or a rat.”

For one thing, pig and sheep organs are similar in size and shape to an adult human’s. And, since they grow relatively quickly, certain organs can be essentially grown to order. Recent advances in genetic engineering make scientists optimistic that they can even genetically tailor organs to be more compatible with their human recipients.

“This is a first step in a long series of stages to eventually get to an actual complete human organ that will develop in a live born sheep,” Insoo Hyun, a bioethicist from Case Western Reserve University who was not involved in the study, told Digital Trends. “It would then hopefully make it all the way to adulthood and make it large enough for transplantation.”

How it’s done

Human-animal hybrids may have a long mythical history, but scientifically they’re pretty new. Just last year, Ross and his colleagues made a splash when they published a report in the journal Cell that showed they’d successfully developed a pig embryo with human cells. The host embryos didn’t have many human cells — just about one in 100,000 — but the survival of even just a few made for groundbreaking research. DNA analysis suggested that the recent sheep embryos reached a ratio of about one human cell in 10,000 cells, according to Ross, which is progress but still not efficient enough to successfully grow transplantable organs.

Here’s how the recent research worked.

To begin, scientists injected human stem cells into an early-stage sheep embryo. At about a week old, they then implanted that chimeric embryo into a female sheep and let it develop for 28 days. After those four weeks, the researchers euthanized the sheep and ran DNA analyses on the chimeric embryos to see how well the human stem cells developed.

Thanks to advances in genetic engineering, scientists can use gene editing tools like CRISPR to create host animals that develop without a specific organ. This way, the injected human stem cells fill the void of the missing organ, and develop into the desired organ as the embryo matures.

“We don’t know which type of human stem cells could have this property of making a chimera.”

“What we’ll need at that location at that specific time are human cells that have to be precisely there to respond to that need for pancreas formation,” Ross said. “And those human cells won’t have competition from the pig or sheep cells. You need the cells at precisely that moment which means you’ll need the cells kind of randomly across the whole body because we cannot yet direct the cells to only be there and nowhere else.”

One of the big questions now is which human stem cells are the most successfully adaptive.

“We don’t know which type of human stem cells could have this property of making a chimera, specifically an interspecies chimera,” Ross said.

Facing controversy

Human-animal chimera studies are controversial but they’re gaining favor. In 2016, the National Institute of Health (NIH) announced plans to lift its moratorium on such research.

Still, animal welfare advocates worry that these studies infringe on the well-being of the test subjects. Bioethicists also worry that these experiments could lead to the development of unusually human-like creatures.

Statistic Brain Research Institute (2017)

An important consideration, as Hyun stated, is “whether or not you are creating large animals that are more or less biologically human in important respects or may have a status that is a little higher morally than a normal sheep.

“There’s the concern that these types of experiments create morally ambiguous beings,” he added. “We know what sheep are and we know what people are, but what about sheep that have large contributions of human cells or an entire human organ? That’s a new thing, where does it fall on the spectrum?”

Hyun said his personal concerns center around animal welfare, that the subjects are living comfortably and being treated humanely.

“The concerns about the personhood of an animal, [as long as] we’re staying away from the brain, is not yet an issue to worry about,” he said.

“I don’t have the statistic for the number of animals slaughtered for bacon everyday but it’s significantly more.”

Ross recognized the importance of these concerns and stressed that all of their research is performed under biomedical research oversight and regulation. However, when it comes to the concern about creating animals that are more or less biologically human, Ross pointed to previous research that suggested host species still grow their species-specific organ, irrespective of the introduced stem cells.

“But at the same time, because we’re scientists, we’re not just going to go with what we believe or expect to happen,” he said “We want to measure that. We want to produce scientific information to inform whether this is something acceptable or not.”

As for animal welfare concerns, Ross stressed that the animals in these cases would be treated humanely and would provide a tremendous benefit to society that, for many, may outweigh the downside.

“If this [research] becomes successful, there is a concern about using animals for human benefit,” he said. “But you have to consider that we use large animals for food, work, clothing, and emotional comfort. I don’t have the statistic for the number of animals slaughtered for bacon everyday but it’s significantly more [than those that would be used for organ transplant]. Several orders of magnitude more. That’s a choice the public will have to make.”

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