SaveSave story

Scientists put human cells in a sheep embryo. Here's what that means.

Illustration: Rebecca Zisser / Axios

Researchers have successfully incorporated human cells into a sheep embryo — the first step in a process that they hope may one day allow them to grow replacement organs in other animals. The advance is one of several recent ones in a burgeoning field that is raising ethical questions.

The bottom line: Advances in the past year are important proofs-of-principle that this is even a plausible approach but an organ hasn't been grown in a large animal.

"We’re a long way away from getting a human tissue in a pig or sheep," says Thorold Theunissen, a stem cell biologist at Washington University School of Medicine. "It's a tantalizing prospect and important that more experiments are done.”

The need: On average, 20 people in the U.S. die each day waiting for an organ and someone is added to the national transplant list every ten minutes, according to the United Network for Organ Sharing.

Key experiments to date:

  • Last year, Hiro Nakauchi from Stanford University's School of Medicine and his colleagues reported they could inject mouse pluripotent stem cells — which are able to form all types of adult stem cells — into embryos of rats that lacked a key gene for the development of the pancreas. The embryo instead developed the organ from the mouse cells. After the rat-mouse chimeras grew into adults, cells from those pancreases were transplanted into diabetic mice and the researchers found the disease was reversed.
  • Also in 2017, researchers reported incorporating human cells into a pig embryo with a relatively low efficiency of about one human cell for every 100,000 pig cells. Pigs are ideal because their organs are roughly the same size as humans and they grow fast.
  • On Saturday, at the annual meeting of the American Association for the Advancement of Science, Nakauchi, Pablo Ross from UC-Davis and Daniel Garry from the University of Minnesota announced they had created a human-sheep embryo. In this scenario, they saw 1 human cell for every 10,000 sheep ones. "It’s still short of what we postulate would be necessary to grow a whole organ," Ross tells Axios. That, he says, requires a contribution closer to 1% of all cells in the embryo.

What's next: Determining where the cells are going in the embryo and what impact they are having, Ross says. He also wants to use animals that have been gene-edited with CRISPR to lack certain organs and see if that helps the introduced stem cells grow in the host embryo. Theunissen and others are trying to determine the best conditions of the stem cells for incorporating them into the embryos — and which embryos are the best hosts.

One ethical concern is that the introduced cells will migrate to the host animal's nervous system, sparking fears of humanizing animals. But Nakauchi says they've been able to direct the cells to specific regions. Ross, too, says it's unlikely because the host embryo is driving the process of development and a sheep or pig doesn’t have the anatomy or right conditions to support something like a human nervous system.

"We aren’t on the brink of seeing half-sheep, half-human animals. This research is going to go slowly because it is difficult to get the cells what you want them to do,"
— Insoo Hyun, bioethicist, Case Western Reserve University's School of Medicine

Still, Ross says, "[W]e need to observe that with science and generate scientific information that will help us make a decision about this approach that we are comfortable with — if it works. ... The final decision will be up to the public."

The NIH currently doesn't fund research involving the transfer of human stem cells to large animal embryos. There is oversight at the university and institutional level — for example, the sheep embryos were allowed to grow for 28 days.

The big picture: Researchers have long tried to understand the environmental cues that turn stem cells into one cell type instead of another and then to replicate those signals in the lab — in hopes of developing therapies for Lou Gehrig's disease, strokes and other conditions. Stem cells remain a bit of a black box but some clues may come from these experiments, Theunissen says. "It's not just about the whole tissue but also the individual cells."

What's next for cancer immunotherapies

A researcher holds a plate used to grow T cells.
Photo: BSIP/UIG via Getty Images

Cancer immunotherapies that trigger a person's own immune system to recognize and attack cancer cells have logged some success in certain patients and with certain types of cancers. "But overall that is a minority of cancer patients," says Antoni Ribas from the University of California, Los Angeles.

Now, researchers are looking to leverage their understanding of what's working and what's not in patients receiving this class of drugs. (Science published a special section about cancer immunotherapy Thursday.)

The challenge: These are new avenues for research but they also spur serious concerns that must be addressed: unwanted and sometimes deadly side effects, unexplained lack of response by some cancers, and questions arising from combining multiple therapies and finding the optimal timing — which can make or break treatment.

The worst flu season in eight years

Note: Activity levels are based on outpatient visits in a state compared to the average number of visits that occur during weeks with little or no flu virus circulation; Data: Centers for Disease Control and Prevention; Chart: Chris Canipe/Axios

This year's flu season caught many experts off guard with both its sustained prevalence and its virulence. At its peak, there was a higher level of flu-like illnesses reported than any other year during the past eight years. Watch in the visual as it hits its peak around Week 18.

Why it matters: Public health officials try to capture this data when developing the next year's vaccines. And, of course, they want to find better ways to prevent severe flu seasons. There's a "Strategic Plan" to develop a universal vaccine to protect against a wider range of influenza viruses, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, tells Axios.