Swine flu may have been circulating among pigs for many years prior to its transmission to humans, said Charles Chiu, M.D., director of the University of California, San Francisco’s (UCSF) Viral Diagnostic and Discovery Center and its Chiu Lab.

Chiu is working on technology to identify viruses including H1N1 (swine flu) more quickly and accurately to avoid or lessen the impact of pandemics like the one we’re now facing. He is working on virus surveillance technology that may eventually sequence the entire genomes of viruses within a matter of hours, providing detailed information about how these viruses are passing through a population and how they are changing in real time.

Chiu envisions a time, maybe in the next five to 10 years, when this type of virus surveillance technology could be cost effective and fast enough to be used by the Centers for Disease Control and Prevention, the United States Department of Food and Agriculture and other public health agencies to identify outbreaks in animals and humans as they happen, even if a virus has never been seen before, Chiu said.

In the meantime Chiu’s lab is collaborating with other researchers and public health agencies to provide information on the H1N1 virus that could help them formulate better vaccines and therapies.
While doing a fellowship on infectious disease at UCSF, Chiu worked with UCSF researchers Joseph DeRisi and Don Ganem, who led the development of the Virochip microarray and deep sequencing technology that Chiu is now using in his lab.  

The Virochip microarray has been credited with identifying SARS (Severe Acute Respiratory Syndrome) as a novel virus in 2003. SARS spread to 37 countries in just a few weeks.

The latest version of the Virochip consists of a glass slide with approximately 36,000 DNA fragments representing all viruses known to man, about 2,500 viruses in total. It can detect the presence of a virus in as little as 12 to 24 hours.

Sharon Hietala, a professor of diagnostic immunology at the California Animal Health and Food Safety Lab at UC Davis, said that many labs are now working with microarrays and gene chip analysis but that, in her opinion, DeRisi is the one who kick started the technology currently used.

“The work done in that lab set the stage,” she said. Although the technology is still a bit too pricy for widespread use in animals, she said that chips are on their way and being tested in animals.

Additionally, Chiu is using research by DeRisi and Ganem on high throughput deep sequencing. By sequencing the whole genome of viruses from different individuals, over time researchers can better understand what changes are happening at a genetic level in the viruses. They can determine if a virus is becoming more resistant, more virulent and how it is spreading. This can be determined as these things are happening, in real time.

“This technology may help prevent something like this in the future,” Chiu said. He hopes it will eventually be used as a routine surveillance tool in both animals and humans. He’s discussing that with various groups, including the California Department of Public Health (CDPH).

“In an ideal world we would look at every animal reservoir that has flu,” said Janice Louie, M.D., section chief for the Viral and Rickettsial Disease Laboratory at CDPH. But even if resources weren’t an issue, Louie said she’s not sure researchers would know what action to take if they did find a new virus. She wonders if it  would mean culling a lot of pig herds?
Louie questions whether the technology Chiu is working on can help us avoid pandemics because flu is so unpredictable, she said. But if it helps us identify viruses that are resistant to drugs like Tamiflu, then clinical trials of other drugs could be accelerated by the U.S. Food and Drug Administration. So, in that sense, while the technology might not help us avoid pandemics, it could certainly lessen the impact and reach of a pandemic.

Louie’s lab shares virus specimens with the Chiu Lab and they meet regularly to explore the discovery of new viruses, she said.

Ian Lipkin, M.D., director of the Center for Infection and Immunity (CII), consisting of 65 investigators at Columbia University, said it’s reasonable to do sentinel testing of animals, but it should be done using the least expensive technology that is sufficiently sensitive to detect microbes in animal specimens. Most investigators use polymerase chain reaction (PCR), which indicates a positive test if pieces of a pathogen’s genome are detected. The CII uses a multiplex PCR method (MassTag PCR) that detects up to 30 different viruses and bacteria for the same cost as a single agent PCR.
Lipkin’s lab houses a World Health Organization center working on diagnostics and discovery and Lipkin is working with colleagues globally as well as the Department of Defense to analyze cases of respiratory disease and to follow influenza virus evolution.

Lipkin’s Lab is also developing what he calls “fieldable versions” for both the PCR technology they are using and for GreeneChips. GreeneChips contain up to one million pieces of genetic material from viruses, bacteria, fungi and parasites that can identify pathogens in human fluid and tissue samples. Access to that type of technology on site where outbreaks of viruses are happening would help with triage and containment, Lipkin said.

The President’s Council of Advisors on Science and Technology issued a report on Aug. 7 stating that H1N1 could cause between 30,000 and 90,000 deaths this year in the United States, potentially triple the deaths from the seasonal flu and will likely be concentrated more in children and young adults.

Given that possibility and the fact that since 1973, more than 30 diseases linked to viruses and bacteria that were previously unknown have surfaced, such as avian flu, West Nile virus, Ebola virus, AIDS/HIV and Hepatitis C, according to the Ontario Agency for Health Protection and Promotion, there is certainly a need for new tools that can alert us to the presence of new viruses. That would afford us more precious time for reigning in the spread and developing effective treatments for those afflicted.

Already, Chiu’s technology has successfully been used to identify viruses in diagnostics, and he hopes that the technology developed at UCSF could one day identify and help combat the even the toughest of future viruses.

Lynn Graebner is a freelance writer in Santa Cruz.