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By Richard Silberman, Writer/Researcher, IBM Communications

Ruhong Zhou, Ph.D., conducts groundbreaking avian flu research on IBM Blue Gene

The next time an avian flu scare strikes — as it did in 2004 and likely will again — the world may be better prepared thanks to the work of Ruhong Zhou, research staff scientist and manager of the Soft Matter Theory and Simulation Group at IBM’s Thomas J. Watson Research Center.

Zhou and his team have been using an IBM Blue Gene supercomputer to anticipate genetic changes in the H5N1 influenza virus (commonly known as avian or bird flu) that might pose a serious threat to human health. Although H5N1 rarely infects the human population, when it does it has an extremely high mortality rate.

In a recent breakthrough, Zhou was able to computationally identify the single mutation in H5N1 that, should it occur, would debilitate antibodies in our immune system from fighting off this deadly flu. Armed with this information, pharmaceutical companies could design a vaccine that would compensate for this mutation and allow people to develop the necessary antibodies to combat H5N1 if they contract it.

“By isolating and anticipating this mutation, we can be proactive in creating a vaccine before the next avian flu outbreak strikes — potentially saving lives and even helping prevent a global pandemic,” Zhou said.

Taking the guesswork out of vaccine design

Influenza can undergo various mutations over a short time period, so trying to predict exactly how a flu strain will mutate next is the first step in vaccine development. It is too costly and time-intensive, however, to do this type of upfront research by trial and error in a traditional lab setting, so Zhou uses computer simulations to do his work.

Blue Gene provides the computational power to rapidly and efficiently simulate mutations at the atomic level so scientists can now predict a mutation with great accuracy and take much of the guesswork out of vaccine design.

Zhou simulated over 100 single and double mutations of H5N1’s hemagglutinin (HA) protein on Blue Gene in order to pinpoint the single, antibody-suppressing mutation he sought. Using all of Blue Gene’s 8,000 processors, it took two days to model each mutation. By comparison, it would take 8,000 days — or 22 years — to run each model on a laptop or desktop computer with a dual CPU.

“We could have never done our research without Blue Gene,” said Zhou, who has a Ph.D. in chemistry from Columbia University, where he currently teaches graduate level courses. “High performance computing of this sort is enabling a new era of breakthroughs in life science and holds great promise for advances in personalized medicine as well.”

Avian flu is an ongoing threat and has the potential to erupt into a pandemic someday. Zhou's work will help the world be better prepared and potentially save lives.

A proactive approach to preventing pandemics

For Zhou, who recently published his findings in Biophysical Journal, this breakthrough is particularly meaningful because of the real promise it holds for public health.

“As scientists, we often do some basic research just for our own curiosity — and achieving the results is gratification enough,” Zhou said. “But this is not just for our own interest; this is something very, very important to human society.”

Along with his avian flu research, Zhou has been using Blue Gene for the past six years to model genetic variations and predict mutations in other influenza strains, including swine flu (H1N1) and Hong Kong flu (H3N2). Zhou hopes the ability to anticipate mutations will prompt the medical community to start preparing preemptive vaccines well ahead of flu outbreaks, rather than responding after the fact (and after lives have been lost), which is the usual practice.

“We need to move from a reactive model of vaccine development to a proactive one,” Zhou said. “Our ability to accurately predict what mutations will happen next should give pharmaceutical companies the confidence to invest in vaccine production early enough to mount a strong defense against a virus and prevent a pandemic.”

Partnerships with government agencies like the Centers for Disease Control (CDC) and with pharmaceutical companies that want to use Zhou’s research to guide vaccine design are essential to realizing the full potential of Zhou’s work.

“With the right funding model and partnerships we can continue to explore influenza strains as well as other infectious diseases, such as HIV,” Zhou said. “I firmly believe that together we can develop better vaccines that will have a profound impact on society’s health and well-being.”

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