How to Be Humane to a Lab-Grown Brain

Part of the brain’s allure for scientists is that it is so deeply personal—arguably the core of who we are and what makes us human . But that fact also renders a large share of imaginable experiments on it monstrous, no matter how well intended. Neuroscientists have often had to swallow their frustration and settle for studying the brains of experimental animals or isolated human neurons kept alive in flat dishes—substitutes that come with their own ethical, practical and conceptual limitations.

Original story reprinted with permission from Quanta Magazine, an editorially independent publication of the Simons Foundation whose mission is to enhance public understanding of science by covering research develop­ments and trends in mathe­matics and the physical and life sciences.

A new world of possibilities opened in 2008, however, when researchers learned how to create cerebral organoids —tiny blobs grown from human stem cells that self-organize into brainlike structures with electrically active neurons. Though no bigger than a pea, organoids hold enormous promise for improving our understanding of the brain: They can replicate aspects of human development and disease once thought impossible to observe in the laboratory. Scientists have already used organoids to make discoveries about schizophrenia, autism spectrum disorders and the microcephaly caused by the Zika virus .

Yet the study of brain organoids can also be fraught with ethical dilemmas. “In order for it to be a good model, you want it to be as human as possible,” said Hank Greely, a law professor at Stanford University who specializes in ethical and legal issues in the biosciences. “But the more human it gets, the more you’re backing into the same sorts of ethics questions that are the reasons why you can’t just use living humans.”

In the popular imagination, fueled by over-the-top descriptions of organoids as “mini-brains,” these questions often center on whether the tissue might become conscious and experience its unnatural existence as torture. The more immediate, realistic concerns that trouble experts are less sensational but still significant. It also doesn’t help that the study of organoids falls into an odd gap between other areas of research, complicating formal ethical oversight. Still, no one wants to see brain organoids’ potential discarded lightly.

The projecting axons of neurons (red) from a human brain organoid grow out across a culture dish. Their nuclei are stained blue.Photograph: Alysson Muotri
Donald O’Rourke, for example, is a neurosurgeon at the University of Pennsylvania’s Perelman School of Medicine who is using organoids, including ones transplanted into rodents, to test treatments for an aggressive type of brain cancer. The ethics of organoid research don’t trouble him at all. “I’m dealing with a deadly disease that kills people in 15 months,” he said. “Here we’ve developed an advanced diagnostic tool to evaluate in real time what therapies might be beneficial. In my mind, that solves ethical problems.”
So organoid science is moving forward. And even if organoids are a long way from feeling pain or becoming conscious, Greely and other ethicists and biologists stress that it’s important to start talking about those possibilities now to steer away from them later. To that end, they’re employing a collaborative approach to bring the science and ethics together early. As a first step, they’re embarking on studies to illuminate the differences between organoids and real brains, and developing benchmarks for comparing them.
Unconscious but Increasingly ComplexThere is nearly universal agreement among those familiar with the field that today’s brain organoids, and any likely to be grown in the near future, will not be conscious. “They’re still very, very primitive and rudimentary compared to even the brain of a mouse,” said Han-Chiao Isaac Chen, a professor of neurosurgery at the Perelman School of Medicine, “let alone the brain of a human.”