December 2003


Global computational grid takes on smallpox threat

Biological weapons have been around for decades. For most of us, it was the stuff of entertainment—novels and movies involving Cold War secret agents. The end of the Cold War didn’t make the world a safer place. Fear of terrorists around the globe gave rise to an unprecedented sense of urgency in how we deal with the threat posed by biological weapons such as smallpox.

In response to the potential threat of smallpox being used as a weapon of bio terrorism, an international consortium of researchers recently completed a massive global collaborative computing project to find new treatment options for the deadly smallpox virus.

Dr. Grant McFadden has led the project at the university and research level. McFadden, an expert on viruses that can cause pox diseases such as smallpox, is the Canada Research Chair in Molecular Virology at The University of Western Ontario and Co-director of the BioTherapeutics Research Group at the Robarts Research Institute.

Speaking at the ORION–-CA*net4 Advanced Networking Day workshop hosted by the University of Western Ontario earlier this month, McFadden drew on his experience with this project to illustrate the enormous power and impact that collaborative computational efforts can have in areas where the size and complexity of the challenge traditionally made researchers shy away.

“I think that most researchers are, like myself, computationally challenged,” said McFadden in an interview. “This project demonstrated to me the enormous potential of research combined with high speed computation capabilities, the kind that ORION provides for Ontario researchers.”

The Smallpox Research Grid

"Viruses are difficult to 'weaponize'," says McFadden. “However, smallpox is a particular concern because it was suspected to have been developed as a bio-terrorism tool by the former Soviet Union and these stocks could have fallen into rogue hands.”

The smallpox virus has an incubation period of one to two weeks and is extremely contagious. It is estimated that thirty per cent of those who get smallpox will die and those who don't may become disfigured or blind. Since smallpox was eradicated in the late 1970s by vaccinating everyone against the disease, preventative vaccinations no longer take place making everyone susceptible to an outbreak.

What the world needs urgently is an anti-smallpox drug in the event of an outbreak. Achieving this requires millions of potential anti-smallpox molecules to be screened against the virus in as short a period of time as possible. That’s where the computational challenges surfaced.

In a truly global response to this problem, the computing power of millions of personal computers was volunteered to this effort by individuals in more than 190 countries. A virtual supercomputer capable of analyzing millions of molecules in a fraction of the time it would take in a laboratory was created by combining idle computing resources. These resources were donated at www.grid.org and coordinated by United Devices of Austin, Texas. The computational grid achieved over 39,000 years of computing time in less than six months.

The Smallpox Research Grid project used specialized computational software to screen 35 million potential anti-smallpox drugs against portions of the protein structure of the smallpox virus in the search for good drug targets. The results of the Smallpox Research Grid project, a ranked list of drug candidates, were delivered to the U.S. Department of Defense at an event hosted by the British Embassy in Washington, D.C in September 2003.

“What we’ve managed to do is narrow that huge number to a few thousand potential molecules that can be considered lead candidates for the next phase of research,” said McFadden. “The next step will be to test these potential drugs in the lab for the ability to inhibit the viral enzyme, called topoisomerase, which was the target of the screen. Once this screen is complete, the short list of drug candidates that remains then needs to be tested in animals for the ability to inhibit the virus.”

The combination of private technology and public participation has attracted the attention of both scientific and political leaders.

McFadden’s lab studies how these viruses that weaken the immune system’s defenses carry out their attack. McFadden was a member of the 1999 Institute of Medicine committee in the United States that evaluated future uses of the smallpox virus for research purposes, and is a member of the current World Health Organization's committee deliberating the fate of the declared variola stocks, the virus that causes smallpox.

In addition to researchers at the U.S. Army Medical Research Institute of Infectious Diseases, which funded the project, essential technologies and services were provided by the University of Western Ontario, Robarts Research Institute, IBM, United Devices, Accelrys, Evotec OAI, University of Oxford, Memorial Sloan Kettering Cancer Research and Essex University.

A copy of Dr. McFadden's ORION-CA*net 4 Advanced Networking Days presentation is available to download at http://www.orion.on.ca/pdf/mcfadden.pdf.


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