After 30 minutes, the rat should have been dead. Sealed in a capsule-shaped chamber, the animal was breathing pure oxygen at a pressure high enough to cause a normal rat to have a seizure in five to 10 minutes. Dominic D’Agostino, a researcher at the University of South Florida, stood by, ready to flush the chamber with fresh air and rescue the creature at the first signs of a problem. But 30 minutes became 40 minutes, and still the rat appeared unbothered. At an hour, D’Agostino could only gaze at it on a video monitor with wonder. “The rat was just kind of staring back at us and grooming itself,” he says.
Shortly before placing the rat inside the chamber, D’Agostino had injected a new, one-of-a-kind molecule down the animal’s throat. Much of D’Agostino’s work is funded by the U.S. Department of Defense’s Office of Naval Research, and this experiment, which he conducted in mid-2011, was his first test of whether the new molecule could help a rat withstand an onslaught of oxygen. The hope was to one day do the same for Navy divers, who can experience devastating oxygen-toxicity seizures on deep dives.
As D’Agostino watched his record-breaking rat relax in the chamber, however, his mind raced through even bigger medical implications. Many people with epilepsy have seizures similar to those caused by oxygen toxicity; if all went well, perhaps his new molecule could reduce those, too. Even more tantalizing, preliminary research on similar molecules had already hinted at possible benefits for patients with a wide range of diseases, including Parkinson’s and Alzheimer’s disease and some cancers.
The substance D’Agostino gave the rat was a lab-created compound that works by increasing levels of ketone bodies, molecules that the liver produces from fat when animals fast or eat very few carbohydrates. Naturally made ketones make it possible to fuel the brain when glucose is running low, a trick designed by evolution to allow our ancestors to survive for long stretches with little or no food. Today, ketones are best known as the driving force behind the ketogenic diet, the low-carb, high-fat health craze that has led many Americans to eat huge slabs of beef and add heavy cream to their coffee.
The keto diet amounts to a strict Atkins diet, and people often turn to it in an attempt to lose weight. The scientific evidence on its effectiveness is limited, but enthusiasts swear by the diet’s power to ward off hunger, increase mental alertness, and boost athletic endurance. Meanwhile, scientists have known for decades that the keto diet can prevent epileptic seizures even when pharmaceutical treatments have failed. But the work of D’Agostino and a handful of other pioneering ketone researchers over the past decade has also led scientists at Harvard, Yale, and other top institutions to consider the diet’s potential to treat other diseases. Siddhartha Mukherjee, an oncologist and the author of The Emperor of All Maladies, a Pulitzer Prize–winning history of cancer science, is among those interested in whether the ketogenic diet could have a role in cancer therapy.
D’Agostino’s impervious rat pointed toward a