Commentary

Combating Biological Threats through Drug Development

Concerns about underground nuclear testing and the effects of ionizing radiation on humans prompted the Atomic Energy Commission to establish a biological research program at Lawrence Livermore in 1963. Since then, the program’s mission has evolved to address changing national needs, while making important scientific breakthroughs in the process. For instance, the early work on radiation led to the discovery of flow sorting and chromosome painting, which enabled researchers to study DNA damage and the creation of chromosome-specific clone libraries in new ways. The Human Genome Project, the largest biological research project ever undertaken, followed these key discoveries.

In the years since 9/11, Livermore biologists have concentrated their efforts on detecting, assessing, and combating biological threats, both natural and deliberately developed. Solving national problems in biosecurity and human health demands highly collaborative interdisciplinary teams working at the frontiers of basic and applied sciences. The Biosciences and Biotechnology Division is the nexus for biology research at the Laboratory. Our biologists also work closely with chemists, engineers, physicists, and computer scientists from across the Laboratory on endeavors such as delivering technologies that rapidly detect a pathogen once it is released, processing samples with possible bioterrorist agents, cleaning contaminated facilities, and treating people exposed to pathogens, to name just a few.

The Laboratory has a distinguished track record in developing and deploying biosecurity and biomedical capabilities. Many of these efforts are enabled by the tools and expertise available through our biology-related capability centers. For instance, Livermore’s Select Agent Center, home to the only Department of Energy Biosafety Level 3 Facility, allows researchers to conduct experiments on a wide range of microorganisms for developing much-needed biodetection capabilities. The Center for Accelerator Mass Spectrometry, a particularly versatile facility, is used to perform a Livermore-developed technique called microdosing, which allows biomedical scientists to safely test in humans whether the active ingredients of a drug are absorbed and how long each ingredient persists in the body. Researchers at the Livermore Microarray Center can analyze and compare the concurrent activity of thousands of genes at a time, advancing research in such areas as cell response to radiation exposure and the genetic makeup of plague-causing bacteria. Finally, the Forensic Science Center is home to nationally recognized experts who often work at the intersection between biology and chemistry in support of various counterterrorism efforts.

Of growing importance to our biological program are Livermore’s world-class computational resources. Only recently have we begun to see computer modeling and simulation approach the level of experiment and capture some of the complexity of biology. We are just scratching the surface now, but future generations of high-performance computing (HPC) systems will serve as an equal and crucial partner to experiment. Accomplishing accurate biological simulations requires significant computational horsepower and advanced codes that have been fine-tuned to run on these machines. Our biologists face a formidable computational challenge in analyzing the reams of data produced by modern biology experiments—an effort well-aligned with Livermore’s growing emphasis on big data analysis.

The tantalizing possibilities that HPC can offer biomedical research are exemplified by the research efforts discussed in the article A New Model for Pharaceutical Research. Here, we describe how Livermore researchers are expediting the development of drugs and medical countermeasures for new pathogens by addressing key scientific barriers in the drug discovery and development process. The current process is not sufficiently agile to respond to unexpected biological threats in a timely fashion. Bringing a drug to market can take 10 years or more, while new threats can arise suddenly. The 1918 influenza pandemic, for instance, may have killed as many as 25 million people in its first 25 weeks. Fortunately, the work our researchers are conducting suggests that portions of this process can be significantly accelerated with the help of HPC-based modeling and computational expertise. More broadly, performing biology research in silico will become increasingly important in the coming years, as Livermore biologists pursue challenging research agendas in the areas of human health, agriculture, and biosecurity.