Talent and Technology Team Up to Fight Pandemics

Picture the international terminal at JFK airport in New York. Every hour hundreds of people are disembarking flights from Hong Kong, London, Reykjavik, and Trinidad. Some catch connecting flights, others join the throng pushing to baggage claim, then get into buses, trains, and taxis headed for the city. All the while, they are sneezing, coughing, holding railings, and rubbing their eyes.

If the current strain of bird flu (H5N1) ever became easily transmissible among humans, this scene would be a global health official’s worst nightmare. Because of today’s frequent international travel, infectious diseases that in days past might be contained to a small geographical area can now spread rapidly around the world.

The threat of a global pandemic of avian flu is what prompted Scripps Research president Richard Lerner to approach IBM with the concept for an innovative partnership. Project Checkmate, announced in the spring of 2006, capitalizes on Scripps Research’s cutting-edge biomedical research and IBM’s super-computing power in order to study the genetic variations of viruses and the responses from the host immune system. The research is aimed at informing strategies for the containment of dangerous viruses far in advance of their actual spread.

What makes viruses particularly difficult to fight is their ability to mutate. Viruses’ replication systems are prone to making errors, meaning that each life cycle produces a different variation of the virus. By the time vaccines and drugs are designed to effectively combat a virus, the virus has taken on a new form.

“If we could predict how a virus such as H5N1 might evolve, we could have antibodies or vaccines ready, and be prepared for whatever move the virus might make,” explains Scripps Research Professor Ian Wilson, who is heading the initiative. “Although the project is currently focused on the imminent threat of the bird flu virus strain H5, the same strategy could be used for any other influenza virus – or even for other viruses.”

Project Checkmate employs the leading talent of both Scripps Research and IBM, as well as Scripps Research’s state-of-the-art biomedical research facility, Scripps Florida, in the race against the next deadly pandemic. Learn more by watching this informational video.

Project Checkmate is a large-scale collaboration, with a variety of research groups tackling different areas. While one team focuses on antibodies that could cross-neutralize against different strains and sub-types, another studies crystal structures of viral components, and others generate libraries of influenza strains.

Dr. Lerner’s team published its initial research last July in The Proceedings of the National Academy of Sciences. Their research utilized a microbiology tool called phage display, which employs bacteria-infecting viruses (phages) as pawns to draw out antibodies and test possible drugs. Lerner’s team inserted phages with a truncated flu gene, then applied them to red blood cells. The phages that latched onto the blood cells were deemed active. Next, the team washed the active flu-phages with a solution of drug-like molecules. By encouraging the molecules that attached to the phages to proliferate and mutate, and then repeating the process a number of times, scientists were able to generate a library of mutations and drug candidates. Lerner and his team anticipate that this relatively simple research method will become an important predictive tool.

Meanwhile, IBM’s team is working to prepare the computational power needed to study how variations in viruses occur from year to year. Simulating the structure of gigantic molecules like hemagglutinin (the H in H5N1) requires computational power that is orders of magnitude beyond what was available even just a few short years ago. Project Checkmate is using IBM’s Blue Gene supercomputer, the world’s fastest, to perform these enormous calculations.

The completion of the Human Genome Project five years ago demonstrated that computer technology is already remaking the field of biological research. Computer modeling allows research that once took months to complete to be run in a matter of minutes. As technology continues to advance, cross-pollination will become increasingly vital.

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