Without such answers, a lot of the hype around biomedical advances becomes wishful thinking. With stem cells, scientists hope to re-grow damaged or lost tissues, but how do we regenerate something when we don’t entirely know what it’s composed of? With gene-editing techniques like CRISPR, we will supposedly hack diseases out of our DNA, but without deep knowledge of our cells, how do we know what to edit?
Our cells are the basic unit of our bodies—the stage upon which our genes enact their dramas. And simply put, “we really don’t know our cells.” says Aviv Regev from the Broad Institute. “And so we don’t know ourselves.”
Consider this fairly basic question: How many types of cells are there in the body? Around 200, according to several introductory pages from the National Institutes of Health. That figure corresponds to major groups, like neurons, heart cells, muscle cells, and more. But if you ask an immunologist, they’ll tell you there are at least 200 types of immune cells alone. Ask an immunologist who specializes in T-cells, and they’ll tell you there are at least 200 of those.
When I met Regev last year, she spent a good 15 minutes talking about all the variations within our cells. There are subtypes upon subtypes upon subtypes, she said. The retina alone contains at least 100 different classes of neurons. To complicate matters, some types of cells can transform into others. And each subtype can exist in many different states based on its environment, its neighbors, its position in a tissue, and the molecules it encounters.
"All of these things, the type and the subtype, the states, the locations, and the transitions … you’d want to know all of them," Regev told me. She let her words hang, and she smiled gently. Because she had a plan to do exactly that: to know everything.
Over the last few years, Regev has been slowly laying the foundations for compiling a Human Cell Atlas—a complete portrait of our cells in all their staggering diversity. It would list every subtype, how they change over time, where they are found, and which genes they switch on. Much like the first fully-sequenced human genome, it would be a resource so fundamental that biologists will use it many times a day without even thinking about it—a comprehensive, searchable Google Maps for the human body.
Creating such a resource is ambitious to say the least, and would have seemed impossible just five years ago. But thanks to technological advances, Regev and others think that the time is right. “The idea has been bubbling,” says Sarah Teichmann from the Wellcome Trust Sanger Institute. “I had talked with someone about this four years ago. At the time, it seemed a bit crazy. Even now, it seems crazy—but also more feasible. And people are willing to consider it.”
That’s partly due to Regev, who has been evangelizing for the atlas since 2014. She is widely respected, and not just for her boundless energy and fierce intellect. “She’s one of the smartest people I’ve ever met, but also intense, perceptive, compassionate and caring,” says Dana Pe’er from Columbia University.