New University-Laboratory Consortium Seeks to Detect Diseases Before the Onset of Symptoms

LIVERMORE - People may soon learn if they have an infectious disease or have been exposed to a bioterrorist pathogen, even before they develop symptoms.

Rapid diagnoses one to two days after infection, rather than waiting one or even two weeks for symptoms to appear, are a goal of a new Biosignatures Consortium started by Lawrence Livermore National Laboratory, the University of New Mexico (UNM) Health Sciences Center and the Center for Biomedical Inventions (CBI) at The University of Texas Southwestern Medical Center at Dallas.

The three-party Biosignatures Consortium has been established under a memorandum of understanding signed by the two universities and LLNL.

"The aim of the Biosignatures Consortium is to provide the earliest possible diagnosis of infection, whether it’s an emerging disease, known disease, or bioterrorism threat," said project co-leader Fred Milanovich of LLNL.

In its initial phase, the consortium plans to study whether diseases can be detected in humans through molecular signatures caused by the diseases even before symptoms develop. Another early focus would be to determine whether bacterial infections can be differentiated from viral infections.

"It’s a national security issue because of bioterrorism, but it’s also a public health issue because of emerging infectious diseases," Milanovich said. "Exactly the same techniques that would be used to look for bioterrorist pathogens can be used to detect emerging diseases or be used in standard clinical practices."

LLNL's part of the project is being funded through Livermore's Laboratory Directed Research and Development (LDRD) program and is one of the largest investments of its kind.

In 2000, Stephen Albert Johnston, director of CBI at UT Southwestern Medical Center, and Rick Lyons, of UNM Health Sciences Center in Albuquerque, initiated a project to see if they could check for diseases before symptoms appear.

Their work, financed by a Defense Advanced Research Projects Agency grant, aimed at developing the instrumentation, sensing systems and computational systems for early disease detection.

"Now with Livermore joining the collaboration, we cover all the bases to accomplish our goals," Johnston said. "We had this vision of what was needed for this project and Livermore's expertise in instrumentation and computation covers the missing pieces."

CBI at UT Southwestern has a noted capability in developing ligands, or binding agents, that allow hundreds of proteins or protein fragments to be rapidly analyzed. This is the critical technology toward the goal of an instrument that can read hundreds of components in the blood.

"We want to make disease detection pre-symptomatic," Johnston said. "We hope to find protein or protein fragments that produce a unique biosignature indicative of specific diseases, including biothreats."

If biosignatures can be found for specific diseases, they could be used in two ways, according to Lyons, associate professor of internal medicine at the UNM Health Sciences Center.

"The biosignatures could be used diagnostically to see if a person has been infected or prognostically to determine whether a patient is responding well to therapy or needs more aggressive treatment," Lyons said.

The Health Sciences Center has a well-regarded capability in infectious diseases and Lyons directs projects on developing models for infectious agents, including those of several biothreat agents.

Two companies - Source Precision Corp. of Boulder, Colo., and Rules Based Medicine of Austin, Texas - are providing analytical capabilities to the consortium.

An External Advisory Committee is being established to assist the Biosignatures Consortium. The committee will be chaired by Dr. David Galas, who led the Department of Energy's Human Genome Project in the early 1990's and is now the chancellor and chief scientific officer of the Keck Graduate Institute in Claremont, Calif.

In addition to Milanovich, other Livermore project co-leaders are Ken Turteltaub, the leader of the Biodefense Division; and Bill Colston, associate leader for Physics' Medical Physics and Biophysics Division.

If successful, the Biosignatures Consortium would add a new capability to Livermore's Chemical and Biological National Security Program, which has already demonstrated a direct DNA signature- based approach to detecting pathogens in environmental samples.

The Laboratory’s Industrial Partnerships and Commercialization (IPAC) office has been involved in the project and its business development aspects. A technology consulting firm, Perspectives, has been hired by IPAC to prepare a comparative market analysis.

The University of New Mexico Health Sciences Center (UNMHSC), located in Albuquerque, is the largest integrated healthcare treatment, research and education complex in New Mexico. As part of a major research university, UNMHSC's research grants and contract awards have increased by 80 percent over the past five years. HSC's Inflammation, Immunology and Infectious Disease Center is a major component of HSC's growing research capabilities.

UT Southwestern is one of the nation's leading medical centers specializing in biomedical research and clinical treatment. UT Southwestern's faculty includes four Nobel laureates, 14 members of the National Academy of Sciences, and 15 members elected to the Institute of Medicine, a national honor reserved for individuals of exceptional distinction and achievement in health sciences research, clinical care and medical education.

Founded in 1952, Lawrence Livermore National Laboratory is a national security laboratory, with a mission to ensure national security and apply science and technology to the important issues of our time. Lawrence Livermore National Laboratory is managed by the University of California for the U.S. Department of Energy's National Nuclear Security Administration.