Keto for Disease Treatment: A Notorious Ex-Con’s Unlikely Role – The Atlantic

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.

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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 workaround to one very big problem in this line of research: Dieting is hard. Most people struggle to stick with a ketogenic eating plan in the long term. If a synthetically formed ketone drink or pill could provide many of the possible benefits of the keto diet without someone having to give up bread forever, it could, in theory, be a huge medical leap.

When D’Agostino first began looking into synthetic ketones, other researchers had already synthesized a ketone molecule, known as a monoester, with funding from the U.S. military. A monoester raises the level of one of the two primary ketones our bodies make naturally. D’Agostino wanted to study the effects of a diester, a molecule designed to elevate two different types of ketone bodies at once. But after more than a year of trying, D’Agostino, who does not synthesize new chemical compounds himself, couldn’t find an affordable way to make the powerful molecule that he would later test on his rat. “Literally, I would be on my phone all day calling people, trying to make this happen,” he says.

The breakthrough came in the fall of 2009, when D’Agostino pursued an idea that was both perfectly logical and perhaps a little bit crazy. He did know of one guy who might be able to make the diester molecule he wanted. The logical part? The man was a brilliant chemist with a proven record of creating novel organic compounds. The slightly crazy part? The man was also an ex-con who had been at the center of one of the biggest scandals in the history of professional sports.

Were D’Agostino a more typical scientist, he might have waited until he found funding for the diester molecule via a more conventional route. But D’Agostino is far from a typical scientist. He played football in high school and, at the age of 44, maintains a Schwarzenegger-esque physique. Stories that circulate about him among his friends and colleagues are mind-boggling. He has claimed that he can hold his breath for almost four minutes and that he once deadlifted 500 pounds 10 times in a row—an impressive set for any weightlifter, but D’Agostino says he did it after fasting for a week. “I have, like, sadistic OCD qualities where I’ll just keep doing it, either until I die or I don’t,” he says.

D’Agostino is soft-spoken and sounded embarrassed when I asked about these superhuman feats. But such extreme acts are a window into his science as much as his personality. He is a well-regarded academic who frequently publishes in respectable scientific publications. At the same time, he is at the forefront of a community of obsessive biohackers who revel in pushing their bodies to places few bodies have ever been pushed. For D’Agostino, ketones, with their appeal to both scientists and biohackers, were a perfect match between researcher and subject.

And so, when a friend in the bodybuilding community suggested that D’Agostino ask the chemist Patrick Arnold for help on his diester molecule, D’Agostino took the idea seriously. Arnold, to be sure, was an unusual option. If there were a Nobel Prize for anabolic steroids, he would have won it, probably more than once. In the summer of 1998, a commercially available supplement that Arnold had popularized, androstenedione—andro, for short—was spotted in the locker of the baseball slugger Mark McGwire. Andro is a prohormone that becomes testosterone after it’s converted in the body, and it was widely thought to be the explanation for McGwire’s astonishing power at the plate that year. (McGwire admitted to taking andro, but the supplement wasn’t banned by Major League Baseball at the time.)

Five years later, another one of Arnold’s creations landed him in a much bigger scandal: He was identified as the man who had created “the Clear,” the nickname for the designer steroid that the now infamous nutritional-supplement company Bay Area Laboratory Co-operative (BALCO) distributed to Barry Bonds, Marion Jones, and other celebrity athletes. The BALCO scandal led to a congressional investigation and even made its way into President George W. Bush’s State of the Union address in 2004. Arnold became known as the “rogue chemist” behind BALCO and spent three months in 2006 in a West Virginia federal prison. That same year, Sports Illustrated ran a profile of him under the headline “Is This Dr. Evil?” The article described his lab as “a modern Frankenstein’s castle.”

Today, Arnold readily acknowledges that he had gone rogue. In the sports-nutrition industry, he says, “being ‘Dr. Evil’ sells products.” But questions about his chemistry annoy him. His lab, he says, was very sophisticated and well kept: “There was nothing ‘Frankenstein’ about it.”

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