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Creepy 'brain in a bucket' study spurs medical, ethical debates

Yale scientists keep pig brains alive outside the body — and that’s just one of several provocative new brain science studies.
Image: Hogs
A pig looks out of its pen at a hog feeding operation near Tribune, Kansas on Nov. 11. 2015.Charlie Riedel / AP file

Three weeks ago, a Yale University neuroscientist, Nenad Sestan, explored the ethical implications of experiments using human brain tissue in an essay in the journal Nature. Then last week Sestan's own brain research was splashed across tabloids under lurid headlines like "Yale experiment to reanimate dead brains promises 'living hell' for humans."

First, a reality check: Sestan’s research used pig brains, not human ones, and nothing was reanimated. Bringing a dead brain back to life remains squarely in the realm of science fiction. But what Sestan and his team accomplished does take science into uncharted waters. Brain research is advancing so quickly that ethicists are scrambling to keep up.

The Yale researchers collected brains from 200 pigs at a local slaughterhouse and rushed them back to their lab, where the organs were kept medically active (though not conscious) by a system of pumps, heaters and oxygen-carrying fluid. The system is known officially as BrainEx and unofficially as “brain in a bucket.”

Sestan declined to speak with MACH about the experiment, pending the publication of results in a scientific journal. Most of what we know about his work comes from news reports of a recent workshop on brain science and ethics convened in Bethesda, Maryland, by the National Institutes of Health.

But Sestan’s work, which he described at the meeting, is being widely discussed and debated by other attendees, including Anna Devor, head of a brain-imaging lab at the University of California, San Diego.

Devor is excited about what Sestan’s research might mean for the treatment of strokes and heart attacks. “There’s a very low survival rate for cardiac arrest, partly because we know so little about what’s best for the brain after blood flow stops for a while,” she says, adding that decapitation in a slaughterhouse is a weirdly useful analog of what happens when the heart stops pumping.

BrainEx shows that it is possible to keep brains alive, both for lab research and, potentially, for human medical therapy. “This result also shows the gray area around the idea of ‘brain death,'” Devor says, and could perhaps someday be used to pull patients back from the shadows. “The hope is that we can transition people in a coma back into a state where the brain is active,” she says.

Human brains in mouse skulls

Just as the BrainEx news was spreading, a group led by Fred Gage at the Salk Institute for Biological Studies in La Jolla, California, announced that they had performed another feat of neural engineering. Whereas Sestan is finding ways to keep brains alive, Gage’s team is growing new brains — using human cells.

The Salk team introduced clumps of human brain tissue inside the brains of lab mice, and got these “organoids” to diversify and develop a network of connections. Previously, brain organoids were grown in test tubes or lab dishes that severely limited their growth. Implanting them into an animal host raises the scientific and ethical stakes.

“The hope is that we can transition people in a coma back into a state where the brain is active."

“Organoids bring us a step closer to understanding and designing better therapies for neurological and psychiatric diseases,” Gage says. “But I agree we need to keep the ethical concerns in the discussion and justify the need or value of these experiments.”

The authors of the Nature essay dismissed the idea that implanted human brains might become conscious — at least not in the near term. But is it ethical to raise human-animal hybrids for research or to harvest their brain tissue? What is the identity of an animal that has bits of human brain in its head? What is its legal status?

Adding a further fantastical twist to organoid research is geneticist Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. Pääbo is inserting genes recovered from Neanderthal remains into human stem cells. His goal is to grow Neanderthal-ized brain organoids and study how their neurons behave.

These Neanderthal-human cellular mashups wouldn’t be actual thinking brains, but they would be the first living bits of Neanderthal-like brain on this planet in 25,000 years.

Talk about bringing life back from the dead.

Ethical high-wire act

Attendees of the NIH workshop sigh in exasperation at the hyperbolic headlines that Sestan’s work has inspired. “The scary kinds of work with humans won’t be done for years, if ever,” says veteran bioethicist Henry Greely, director of the Center for Law and the Biosciences at Stanford University.

“The scary kinds of work with humans won’t be done for years, if ever."

But even research involving animal brains raises ethical questions, and the moral landscape quickly turns slippery when human brains are added to the mix. “Although we can learn much from pig brains, the most valuable information would come from human brains kept intact in this way,” Greely says. “We don’t know whether that can be done and, if so, whether it should be done.”

Sestan kept his pig brains alive for just a day and a half. But he reportedly told the scientists at the Bethesda meeting that it might be possible to keep them going indefinitely — and even to restore the kind of electrical activity that gives rise to an animal mind.

If such techniques could be applied to humans, it might mean that an inactive, seemingly dead brain could possibly be revived. “That is restoring a human being,” Sestan told MIT Technology Review. “If that person has memory, I would be freaking out completely.”

No one knows if such things are possible, but they seem closer to reality than they did just a few weeks ago — which is why scientists are having urgent conversations right now.

“The ethics depends on the science,” Greely says, “and we are in the early stages of figuring out what the science will and will not be able to do.”