“Mountains to Climb”

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The Story

“Mountains to Climb”
http://www.nature.com/nm/journal/v16/n11/abs/nm1110-1176.html [abstract; subscription required for full access]
by Brendan Borrell
Nature Medicine, November, 2010

The Pitch

Michael Callahan’s Quest to Conquer Mountain Sickness

I’m writing to propose a profile on DARPA program manager Michael Callahan and his mission to cure altitude sickness. Most researchers featured in Nature Medicine are successful academics, but the 46-year-old Callahan has had an unusual career path from frostbitten mountaineer to emergency medicine doctor to the head of some of DARPA’s most ambitious pharmaceutical projects.

In March, Callahan’s program quietly began funding researchers at Duke University, the University of Colorado at Denver Medical School, and Colorado State University in an effort to overcome the effects of altitude with a single pill — an effort that will be carried into Phase 2 clinical trials within a record-breaking 2 years. That accelerated timeline will not only serve as a model for the Food and Drug Administration, but as a pilot project for DARPA’s grand initiative to revolutionize US manufacturing.

Hypoxic disorders threaten not only mountaineers but hospital patients with compromised lung function and soldiers and helicopter pilots in high elevation combat zones like Afghanistan. Soldiers stationed at 6000 feet must be ready to fight an enemy at over 12,000 feet with 85 pounds of gear. “We lose that foot race every single time,” says Callahan. He says pilot studies in 2008 and 2009 have already showed promise in activating biochemical pathways that boost hemoglobin levels, expand blood vessels, and increase natural levels of erythropoietin, the performance-enhancing drug abused by Tour de France cyclists.

Sound crazy? There is some indication in the medical literature that it could work. In 2007, a Mount Everest climber named Brian Smith had just recovered from high altitude pulmonary edema (HAPE), and was forced to descend after a failed summit attempt. Most climbers
who develop HAPE put off the climb for another year, but Smith was determined. He took a puff from a steroid inhaler, and swallowed a dose of Viagra along with the glaucoma medication Diamox. A week later, Smith conquered the mountain and his medical case study, which was published last year in High Altitude Medicine and Biology, has become an inspiration for scientists trying to tackle disorders related to low oxygen.

For Callahan this dream is the very reason he joined DARPA in 2005. After training at Harvard Mass General Hospital, he got into disaster management and mass casualty care. He helped clean hospitals in Hong Kong during the SARS outbreak and has deployed to Angola
and Democratic Republic of Congo following the Marburg outbreak. But he’s a climber at heart. “If you saw my x-ray you’d be impressed,” he says, “I have so much metal in me from climbing accidents.” In 1993, he and David Irwin nabbed the high altitude record for being stranded at 21,000 feet for 11 days during a storm. His fingernails had grooves in them and his hair had a stripe without pigment because his body shut down. It took him two months to recover.

To kick off the next phase of the project, Callahan’s former climbing partner Irwin, now a physiologist at UC Denver, has begun testing a cocktail of up to 5 known drugs in rodents. “I’m buckling my seatbelt,” he says. Meanwhile, Duke workers are developing a technique to load blood cells with nitrous oxide to stave off HAPE and its more deadly cousin, high altitude cerebral edema (HACE). Other key players include Joseph Bonaventura, the inventor and physiologist who developed the first aquatic lung. The ultimate challenge for the team is to wrap all this up into small-molecule drug that is safer and more effective than cocktails containing Diamox, which causes dangerous allergic reactions, dehydration, and other side effects.

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