‘It is a balance’: Scientists grapple with ethics of cutting-edge stem cell research

SAN DIEGO — When biologist Alysson Muotri started tinkering with tiny balls of nerve cells in the lab more than a decade ago, his goal was simply to understand early brain development and neurological disease. He didn’t realize he was stumbling into an ethical minefield.

His University of California, San Diego, team found that when human stem cells were grown into so-called brain organoids in the lab, these tiny 3D structures produced regular waves of electrical activity that resembled what researchers see in a full-size human brain when they place electrodes along a person’s scalp.

These brain models were a useful tool to better understand conditions such as autism and schizophrenia, which could help researchers develop and test new treatments. But the work raised profound questions. What happens if brain organoids become conscious of their own existence? Would these cell growths be classified as people, animal models, or something else?

There is no evidence researchers are there yet, Muotri cautioned. But he said it’s probably just a matter of time before brain organoids become large and complex enough to develop some level of consciousness. “I personally think it’s inevitable to get there. But some people think this might be too early to discuss and we shouldn’t because the funding agencies might get scared, the public might get scared, and that might create an unnecessary roadblock for research,” he said. “It is a balance. And how to navigate that? I don’t have the right answer.”

Muotri and other leading stem cell scientists gathered last week at the Sanford Consortium for Regenerative Medicine to grapple with the implications of their work and take questions from the public. Their conversation was wide-ranging, touching on everything from how early and openly researchers should talk about the ethical risks of their work to the pros and cons of dwelling on worst-case scenarios.

There were more questions than answers. And many of the possibilities researchers considered remain hypothetical. But that can change quickly, noted moderator and Arizona State University bioethicist J. Benjamin Hurlbut, who pointed out that scientific advancements can cause these discussions to go “from prematurity to being behind the eight ball instantly.”

Thursday’s panel followed an opening presentation by Jacob Hanna, a researcher at Israel’s Weizmann Institute of Science. Hanna’s team has spent years deciphering the chemical cues that give embryonic stem cells their uncanny ability to grow into all the parts of a living organism, from the cells that keep your heart thumping to the neurons that keep your brain crackling with electrical activity.

His lab recently had a breakthrough. They devised a way to grow mouse stem cells into what they call synthetic embryos, complete with a beating heart and the beginnings of a brain and intestines. These embryos, created without sperm or egg, grew in the lab to the point that mouse embryos would typically reach after 8.5 days in the uterus.

It’s an advance that paves the way for scientists to understand how early development happens — and how this process can go awry. The study also raises the distant possibility of one day using this approach to grow whole organisms in the lab, possibly even people. But that’s not the goal of Hanna’s research, and he cautioned that focusing on misuse of the work can do more harm than good.

“You don’t ban nuclear physics because somebody can make a nuclear bomb,” he said. “There’s a benefit that you regulate.”

Rather than describe stem cell research in binary terms as ethical or unethical, Hanna thinks it makes more sense to talk about the balance between risks and harms. He pointed to the development of drugs and vaccines as an example, noting that these public health tools can be life-saving even though a small percent of people can have serious side effects.

All of the panelists acknowledged that they’re navigating uncharted territory. Many of the current limits on stem cell research simply come down to funding, pointed out Matthew Porteus, whose lab at Stanford University works on editing the genomes of stem cells. But that at least places some guardrails on the work of academics reliant on funding agencies such as the National Institutes of Health or California Institute for Regenerative Medicine. In the private sector, however, Porteus warned that companies aren’t constrained by these soft limits.

“The things I’m most worried about are not what’s going to happen in academics,” he said. “I’m worried about the very rich Silicon Valley tech bro, who decides that they’re smarter than the world and they’re going to do something that maybe the rest of us don’t believe is appropriate.”

Panelists called for transparency and public dialogue, pointing out that understanding laypeople’s concerns can help researchers find experimental solutions that allay those worries without stifling science. For instance, Hanna said, researchers may in some cases be able to work with so-called developmentally restricted stem cells, which can’t develop brain tissue or a beating heart.

And not every conversation need be contentious, he pointed out, citing a personal story as an example. After Hanna’s lab published two of their major embryonic stem cell papers, he received phone calls from an unexpected source — the head of the Greek Orthodox Church in Israel.

The second time, Hanna worked up the nerve to ask the religious leader whether he understood the scientist’s research, and what he thought about it.

“He said, ‘In my opinion, God is allowing you to grow stem cells from an embryo. And since he has given you that ability, you should try to make benefit from it,’” Hanna recalled.

The conversation didn’t leave Hanna with any illusions that his work is controversy-free. But, as he said to the crowd, it “gave me an example that you can get very interesting opinions. And this encouraged me to just talk more, as much as possible.”