Don Ganem (left) and Joe DeRisi have had a promising first hit with their virus chip, uncovering an intriguing link between a retrovirus and prostate cancer.

When a new x-ray taken a few days later showed that her lungs were even more clogged, she was admitted to the hospital and placed on two more antibiotics.

But her condition continued to deteriorate. On the third day she was unable to breathe and had to be placed on a ventilator. Hospital physicians desperately tested her blood and the fluid in her lungs for infectious agents—they even did a lung biopsy looking for suspicious bacteria, fungi, and viruses. “We went through every test we had in the lab,” says Bruce Patterson, the director of virology at the hospital and an associate professor of pathology and medicine at Stanford School of Medicine, “but everything came back negative.”

On the woman’s fourth day in the hospital, Patterson called Joseph L. DeRisi, an HHMI investigator at the University of California, San Francisco (UCSF). Patterson and DeRisi had previously talked about a new device DeRisi had built, a microarray spotted with DNA fragments that can detect DNA sequences from all known viruses. Did he think it could determine what was killing the woman? Patterson asked.

Within a few hours, a medical courier was driving a sample of lung fluid up Highway 101 to DeRisi’s lab in UCSF’s new Mission Bay campus just south of downtown San Francisco. Within a few days, Charles Chiu, a clinical fellow working jointly in the laboratories of DeRisi and fellow HHMI investigator Don Ganem, used the microarray to make a diagnosis. The woman was infected with parainfluenza 4, a virus not previously known to cause acute respiratory failure in healthy young adults.

By that time it was too late to give the patient any more medications, but, miraculously, she lived. Her body got the infection under control. Within a few days she was taken off the ventilator, and 2 weeks later she went home.

This woman was lucky, DeRisi and Patterson agree, but relying on luck isn’t good enough. “If her doctors had known that it was parainfluenza 4 early on in the hospital stay, treatment decisions would have been different,” DeRisi says. “There would have been no reason to give her all those antibiotics plus an open-lung biopsy, which has some pretty drastic potential outcomes associated with it.” As a result of that case, Patterson set up what he calls a SWAT team to deal with the handful of patients who show up in Stanford’s hospital each year with infections that cannot be identified. When existing tests come up negative, samples would be sent to DeRisi’s lab to look for unexpected viral infections.

After all, if doctors don’t know what is making a person sick they can’t propose the best possible therapies. “It’s shooting in the dark,” DeRisi says.

Photo: Olivier Laude

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