Commentary

Team Science Successfully Identifies 6,000 Bugs Simultaneously

Since its inception more than 60 years ago, Lawrence Livermore has earned a reputation for technical advancements made largely through “team science,” a strategy successfully pioneered by E. O. Lawrence. In more recent times, this philosophy has been proven once again successful when biologists, engineers, and computer scientists teamed up to deepen understanding of human cells and their response to not only agents of disease (pathogens) but also environmental insults such as radiation and chemical agents.

Long before the biotechnology industry took off, Livermore multidisciplinary teams were designing high-speed electrophoresis systems for analyzing biological samples based on their size and electrical charge, developing automated high-speed flow systems for sorting and analyzing chromosomes, and unraveling the secrets of chromosome 19 as part of the Human Genome Project. More recently, multidisciplinary teams have simulated for the first time the electrophysiology of the human heart, developed an implantable retinal prosthesis, and formulated a West Nile Virus vaccine using Livermore’s breakthrough nanolipoprotein technology.

As described in the article A Faster and Cheaper Method to Detect Agents of Disease, the latest development by such a team is the Lawrence Livermore Microbial Detection Array (LLMDA). This compact system can detect and identify within 24 hours all bacterial, viral, fungal, and protozoan pathogens for which the genome is known—about 6,000 species and strains. LLMDA uses probes consisting of short stretches of RNA or DNA to help uniquely identify the pathogens contained in a clinical or environmental sample. These probes are selected using a set of algorithms developed by Livermore bioinformaticists.

LLMDA has a wide range of applications in such areas as public health, biodefense, and product and food safety. In particular, our bioinformaticists have been on the front lines of the nation’s biodefense effort since 2001. Because early detection and unmistakable identification are crucial to limiting the potentially catastrophic human and economic costs of a bioattack, Livermore researchers have developed new methods to quickly identify pathogens that could be used to sicken or kill urban populations, livestock, or crops.

The concept of a computerized system to scrutinize a pathogen’s genetic code and select telltale portions for identification began in 2000 when we laboriously developed a method for detecting the bacterium that causes anthrax. This work continued when we developed assays for detecting likely bioterrorism agents as part of a biosecurity system deployed by the Department of Homeland Security at the 2002 Winter Olympic Games in Salt Lake City. Our team reasoned that an automated method could compare targeted pathogen genomes against all other sequenced microbial genomes to reveal which regions of DNA were unique to the pathogens of interest. With Laboratory Directed Research and Development funding, scientists developed a computerized process that has now reached its fullest potential to date with the LLMDA system.

LLMDA dispenses with the need to wait days or even weeks for positive identification of one or many pathogens. Such speedy turnaround could save many lives in the event of a bioterrorist attack or a deadly pandemic such as the 1918 flu that killed more than an estimated 50 million people worldwide. The device also could realize significant cost savings in routine health care by readily identifying bugs causing the common cold, influenza, and other sicknesses.

The new detection system is a fine example of translational research, which applies basic science findings to practical applications that enhance human health. Our translational research portfolio is packed with similar efforts. For example, we are working on a radically different method to test the safety and effectiveness of potential medical countermeasures to biological or chemical attacks. Traditionally, promising new treatments are tested first in time-consuming animal tests. However, animal models are not always accurate predictors of human response. A team of engineers, chemists, and biologists is creating a system that combines human cells, tissue engineering, and microfluidics to reproduce the human physiological response to neurological toxin exposure. We call the device the In Vitro Chip-Based Human Brain Investigational Platform, or iCHIP, and it lays the foundation for the ultimate objective of using human tissue–based assays to rapidly assess new drugs.

Devices such as LLMDA and iCHIP represent Livermore’s continual strive toward innovative applications of science and technology that make a difference for the nation.