In a lab in the Netherlands, Jeffrey Beekman is testing drugs on people with cystic fibrosis—sort of. He's not giving the patients themselves any medicine; instead, he's building small replicas of their organs using their own cells. He's creating miniature versions of them in a dish.
Cystic fibrosis, an incurable, life-shortening genetic disorder, is caused by mutations in a single gene called CTFR. These genetic faults lead to unusually thick mucus and other bodily fluids, which clog a patient's airways and pancreas. There's no cure, but a new drug called Kalydeco can help people breathe more easily by rectifying the problems caused by CTFR mutations. When the U.S. Food and Drug Administration approved Kalydeco, in 2012, it was billed as the year's "most important new drug" by Forbes.
But Kalydeco doesn't work for everyone with cystic fibrosis. The disease can be caused by almost 2,000 different mutations in the CTFR gene, which vary considerably in their effects. Some cause mild symptoms in just one organ, others trigger full-blown cystic fibrosis. On its own, Kalydeco can treat people with eight of these mutations, who account for 5 percent of the 85,000-strong patient pool. When given with another drug, Orkambi, it might also help the 45 to 50 percent of patients with the most common mutation, F508del.
Not bad, but that still leaves a lot of people without options, especially if their mutations are very rare. To see if drugs like Kalydeco and other CFTR-modulators can help these underserved patients, doctors would need to run clinical trials. But that's almost impossible, says Beekman, because there are so few of these patients, and they're scattered throughout the world.
His solution was to build organoids—three-dimensional mini-organs that are grown in the lab from stem cells. Over the last 8 years, scientists have built organoids of retinas, stomachs, livers, kidneys, and even brains. These blobs recapitulate many of the complex features of their parent organs, so you can use them to study how those organs form normally, and how that process goes awry in genetic disorders.
The crucial thing about organoids is that they are personalized blobs. They're made from an individual's cells, so they have all the same mutations that person has. They're not just brains and stomachs in a dish, but your brain and your stomach in a dish. And scientists can use them to predict not just how people will cope with a new drug, but how you specifically will respond.