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DeRisi Lab Uses its Viral Microarray To Help CDC Zero in on SARS Mystery

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There are those who say luck is only a bystander at the intersection where opportunity meets preparation.

Joe DeRisi, an assistant professor of biochemistry and biophysics at the University of California, San Francisco, and a microarray pioneer who earned his PhD at Stanford in the lab of Patrick Brown, might be one of those people. Last week, he was at that intersection when the US Centers for Disease Control called on his lab to help draw a target on the mystery disease called SARS (Severe Acute Respiratory Syndrome).

In November, DeRisi and members of his lab published a paper in Proceedings of the National Academy of Sciences entitled “Microarray-based detection and genotyping of viral pathogens, “outlining a microarray research application they developed over the course of two years.

What the paper described can now be considered a medical sleuthing tool, a microarray that contains all the known viral sequences, and a method for highly parallel viral screening.

On March 22, a Saturday, the lab produced — in a 24-hour-period — a match against some of the 12,000 different viral probes on DeRisi’s home-brew microarray, using DNA samples from patients infected with SARS sent from the Atlanta-based CDC.

The DeRisi analysis confirmed what two other labs, using different assay methods, found: That the virus in the samples belonged to the coronavirus family.

DeRisi will tell you that the illuminated spots on his microarray slide do not mean the coronavirus is the agent of causality for SARS, but the information does help scientists more finely tune their discovery efforts, which are ongoing. And, it is an unusual application of a microarray, one that DeRisi envisioned when he started the project.

As this edition of BioArray News went to press, the World Health Organization was still working to identify the agent of causation of this sickness that, as of Monday, had killed some 61 people among over 1,600 cases identified globally. It is a disease that apparently originated in Asia and then spread throughout the globe.

On March 31, a World Health Organization official, in an article published internationally, said the agency and its collaborators were close to identifying the virus — in a matter of days or weeks.

“Much laboratory work continues here at CDC and in a WHO-supported network of laboratories working worldwide, to continue to try to sort out the cause of this illness,” Jim Hughes, the director of the National Center for Infectious Diseases, said on March 27.

The DeRisi lab was part of that global network of CDC collaborators called on to provide microarray analysis, PCR, or electron microscopy.

“We sent the DNA out to a laboratory at [UCSF] so they could do the absolute state-of-the-art probe for virus genes and help us identify the cause,” Julie Gerberding, director of the CDC, said in a March 24, media briefing. Gerberding said the CDC had tissue specimens from four patients.

The results produced by the DeRisi lab, and the others, helped the CDC form a hypothesis pointing to coronavirus as the cause of SARS, Gerberding said.

“Right now, for us, this is a hypothesis,” said Gerberding. “It is our leading hypothesis based on careful science that has been conducted by some of the world’s best scientists and our collaborators around the world, but there are a lot of other potential explanations for what we’re finding here, and we are exercising caution and not being dogmatic that we have the answer.”

Meantime, DeRisi goes back to his lab bench, envisioning new uses for his microarray, and preparing for the next intersection. BioArray News caught up with him last week to talk about his microarray and his work. See Lab Report, below.

— MOK

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