Scientists Have Just Created Human-Sheep Hybrids

Scientists have recently managed to create a human-sheep hybrid, bringing them closer to creating artificially grown organs for use in organ transplants. The research project involved introducing human stem cells into sheep embryos, and the resulting sheep embryos were approximately 0.01% human genome.  The results of the research were project were recently announced at the American Association for the Advancement of Science.

The embryos were destroyed at 28 days into development, but they still managed to bring researchers closer to possibly developing human organs to give to transplant recipients. There is a substantial need for donated organs in the US, with six people being added to organ donation waiting lists every hour in the country. Thousands of people die every year waiting for an organ donation. Various projects have been created to artificially increase the number of organs available for those waiting, including 3D printing organs, creating mechanical organs, and in this case, creating organs in pigs or sheep.

Creating Artificial Organs From Animal Embryos

Dr. Pablo Ross was part of the team working towards the development of human organs with animal surrogates. Ross is from the University of California, Davis, and he says that even today’s best-matched organs don’t tend to last very long. This is because the immune system of the recipient attacks them. The scientists hope that the research project will enable them to create organs artificially tailored to the recipient, saving lives.

Researchers isolated adult stem cells from humans and placed them into sheep to make the human-sheep chimeras. Stem cells are cells which are capable of developing into any type of cell the body needs. After isolating the stem cells, the scientists injected them into the embryo of a sheep. This is a difficult process to get right, as it involves tweaking the DNA of the stem cell so that sheep organs aren’t grown and that the inserted stem cells begin developing instead.

This isn’t the first time that scientists have experimented with the creation of organs in animal-human hybrids. Last year, researchers used stem cells to grow the pancreases of mice within rats and then managed to transplant the organs into diabetic mice, treating their diabetes. Researchers at the Salk Institute then managed to keep the embryos of pigs which had been injected with human stem cells alive for up to 28 days. Though the achievement was impressive, the level of human cells in the pig embryos was quite low, only about 1 in 100,000.

Photo: Terese Winslow, National Institutes of Health

Organ Rejection Issues

Ross and the rest of his research team have managed to fine-tune the procedure for implanting stem cells into animal embryos, leading to higher levels of human cells than in previous experiments. Ross says that only about 1 in 10,000 cells in the sheep embryos were human. Ross estimates that for the embryo to develop usable organs, the cells of the embryo would have to be about 1% human instead of the 0.01% that they are now.  This means that although the level of human cells is much higher than scientists were able to achieve in the pig-human chimeras, there’s still quite a long way to go before these organs could be used in transplantation.

There’s also the issue of immune rejection to find a solution for. The human body already rejects organs from other humans, and extra steps must be carried out to ensure that the organs could work with humans. Scientists would need to implement mechanisms which ensure that any remaining bits of animal viruses are removed the DNA of the sheep or pig. Odds are that the easiest way to achieve this would be to use CRISPR or Cas-9 genome editing. CRISPR functions by identifying short RNA sequences and then matching them with sections of DNA. When the section of targeted DNA is found, it can be edited using specific enzymes. This form of targeted genome editing has proven extremely successful, and it has a wide variety of applications.

Ross and his team believe that these issues could be overcome quickly if the research received more funding, but there are issues that prevent this. One issue is the ethical concerns that naturally come along with any research proposing the combination of human and animal DNA. Currently, the U.S. National Institutes of Health has a moratorium on funding research projects involving animal-human hybrids. The NIH is considering lifting the ban at some point, but for now, all research done by Ross’ team will have to be funded by private donors.

A culture of human embryonic stem cells. Photo: Public Domain

Ethical Concerns

There are numerous ethical concerns surrounding the type of research Ross’ team is doing. Some people are worried that the introduction of human cells into animals may create pigs or sheep with more human features, such as human-like faces or even more human-like minds.

Ross’ team say they are sensitive to these concerns and want to proceed very cautiously. Ross says that while the team can target the human cells to only construct specific organs, they still want to be careful.

Says Ross:

I have the same concerns… Let’s say that if our results indicate that the human cells all go to the brain of the animal, then we may never carry this forward.

One of Ross’ collaborators, Hiro Nakauchi, echoed Ross’ caution and says that although the human cells in the embryo are at very small levels, they are still conducting tests to make sure the human cells don’t end up in either the animal’s brain cells or gonads.

Beyond the concerns about human and animal cells mixing, there are also moral questions about the ethics involved in creating animals for the sole purpose of having its organs used to sustain humans. As with any research involving creating animals for the purposes of experimentation, controversy abounds. As research into these kinds of artificially grown organs continues, no doubt the ethical debate will heat up as well.

Ross understands the controversy but argues that its wrong to not take some kind of action that could give hope to those who need organs. Despite the controversy inherent in the research, Ross is optimistic that it could save lives. Ross says that while none of the approaches to getting transplant patients organs are perfect, it’s imperative we explore all possible options to help those who need organs.