A Single Test to Rule Them All

Joseph DeRisi (center) speaks with colleagues in the lab. Photo by Steve Babuljak.

Joseph DeRisi (center) speaks with colleagues in the lab. Photo by Steve Babuljak.

Over a 10-month stretch in 2012 and 2013, Joshua Osborn, then 14, of Madison, Wisconsin, found himself in the hospital three times and in his doctor’s office many more. His symptoms were baffling and ever-changing: first, a fever and headache; next, light sensitivity and eye pain; later, fatigue, unexplained weight loss, and seizures.

A host of tests failed to shed light on the cause, and his condition worsened. Eventually, Joshua was put in a medically induced coma and, in a fit of desperation, his doctor, James Gern, MD, reached out to Joseph DeRisi, PhD, chair of UCSF’s Department of Physics and Biochemistry and Gern’s collaborator on an earlier research project, for help.

Gern knew that DeRisi and his colleagues at UCSF – chief among them, Charles Chiu, MD, PhD; Steve Miller, MD, PhD; and Michael Wilson, MD – were hard at work validating software that could quickly compare a patient’s DNA sample with sequences belonging to pathogens. The process, known as unbiased next-generation sequencing, enabled the team to rapidly identify the cause of any infection but was not yet approved for clinical use. He hoped the technology could help Joshua.

Physicians don’t have to wait to confirm results. When every minute counts, they can immediately act on the data to guide treatment decisions.

MICHAEL WILSON, MD, Debbie and Andy Rachleff Distinguished Professor in Neurology

Less than 48 hours after the UCSF team received a sample of Joshua’s DNA and enrolled him in their research project, they had a diagnosis. Leptospira, a potentially lethal but eminently treatable bacterium, was to blame for his ailments. Armed with a diagnosis, Gern was able to administer penicillin, and the swelling in Joshua’s brain began subsiding. Two weeks later, Joshua was walking again, and 76 days after he was first admitted to the hospital, he was home.

The case shed light on the promise of unbiased next-generation sequencing technology, but experts cautioned it would be many years before the test could lead to results with immediate clinical applicability for normal patients.

That number is growing, as is the usefulness of the unbiased next-generation sequencing. The UCSF team is working diligently to expand the clinical applicability of the technology and hopes in the near future to validate it for use in patients with infections of the lung and bloodstream, which together impact more than 2 million Americans each year.

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