Bill & Melinda Gates Foundation

Innovation: A New Lens on Child Nutrition

March 13, 2018

You’ve probably never heard of Environmental Enteric Dysfunction (EED), even though many experts believe that it’s one of the major reasons why hundreds of millions of people in developing countries suffer from cognitive or physical disabilities. The problem is, EED is a mystery: We know very little about what causes it or how to treat it.

Here’s what we do know. In EED, the villae—projections in the small intestine that look like little fingers—get flatter and shorter. This reduces the surface area of the small intestine, which in turn limits its capacity to absorb nutrients. In other words, EED makes it much harder for children to extract essential nutrients from food. The resulting malnutrition makes them more susceptible to infections, which further exacerbates their EED and creates a terrible loop that produces children who are routinely sick and whose bodies and brains never develop fully. According to Dr. Guillermo Tearney, a professor at Harvard Medical School with whom we’re partnering to answer the riddle of EED, the disease could be “at the root of why there’s poverty in the world.”

Part of the reason EED is so elusive is that the only way to study it is with an endoscopy, a procedure that’s too expensive and too invasive to perform frequently on adults in poor countries and too risky to perform on young children in any country. As a result, the best evidence we have about EED comes from endoscopies that were done almost 50 years ago.

But Dr. Tearney and his team at Massachusetts General Hospital may have found a workaround. Dr. Tearney is a pathologist, which entails looking at dead tissue under a microscope, but he’s dedicated his career to pioneering what he calls in vivo microscopy—looking at living tissue in living human beings. Dr. Tearney also has a Ph.D. in electrical engineering, and he used that background to create a tiny capsule with a camera that people can swallow to help diagnose and treat Barrett’s esophagus, a precursor to esophageal cancer. In short, he’s an expert at getting cameras into people’s bodies, which made him a great researcher to work on EED.

Now he’s developing an even less-intrusive device that could work in an infant population, so we can see what’s happening in their intestines. The device starts as a tube two millimeters in diameter—the thickness of a piece of string—one end of which goes through the nose, down the throat, and into the stomach. Once it’s there, the end inflates into a capsule one centimeter wide and 1-2 centimeters long, giving Dr. Tearney a direct line through the tube to the stomach. From that point, he can guide a tiny imaging device down the tube and into the capsule, push the capsule down into the small intestine, and take pictures at microscopic resolution.

In fact, the capsule may be even more effective than taking biopsies of the intestine: Researchers believe that EED comes in patches, which means that biopsies of scattered tissue could miss it entirely. Dr. Tearney’s device, meanwhile, provides a continuous 360-degree picture the whole way down. Eventually, he’ll be able to see not just whether the villae are blunted, but whether certain pathogens are present or individual cells are damaged.

The capsule’s imaging capabilities, however, are only part of what Dr. Tearney hopes it will be able to do. Once you have a portal to the intestine, you can send any device that’s small enough down the channel. He’s working to develop a tiny device to take biopsies, which would allow researchers to do genetic and microbiome analysis of the intestine. He may also be able to collect gut content samples.

Dr. Tearney is already conducting safety studies of the capsule on adults in the United States and Pakistan. Assuming those studies prove the device safe, he’ll test Pakistani adolescents, then children. Appropriately, the regulatory requirements get stricter the younger study subjects are, but he hopes to have an approved device in two years.

A device that allows us to take pictures of babies’ small intestines is the beginning of work on EED, not the end. But it’s a good start. Right now, the only way to test whether a treatment for EED is working is to wait years to see whether children are stunted or cognitively impaired. Even then, we have to make assumptions about why (or why not) a child’s growth was abnormal. With the capsule,  researchers can evaluate the results of different interventions to determine precisely how they’re impacting the villae and other histological aspects of the intestine.

It’s daunting to realize that one of the biggest causes of illness and death in the world is a condition we know so little about. But Dr. Tearney and his team are making it possible to see, both literally and figuratively, what we’ve never seen before.

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