Global influenza laboratory on the horizon

Worldwide, the flu kills between 500,000 and one million people per year; millions more are hospitalized and suffer from secondary bacterial pneumonia. It can also have drastic effects on livestock and wild animals.

No Buck Rogers
To get a better handle on the virus, efforts are under way to develop a high-throughput, global influenza laboratory to improve disease surveillance and control. Scientists say that one could be fully operational in five years for a cost of $45 million, and they are soliciting the federal government and private sources for the money.

"The power of all this is that the building blocks are all there," said Scott Layne, MD, an epidemiologist at UCLA who spoke about the plan at the recent American Association for the Advancement of Science meeting. "This is putting technology together in a new way, not stretching capabilities. It is not Buck Rogers and Flash Gordon."

The proposal would take advantage of the existing global influenza surveillance system that the World Health Organization maintains, and the Department of Agriculture's collection capabilities. It would integrate biologic, engineering, and information technologies that already exist into a centralized facility and make them available via the Internet. Researchers would collect samples from people or animals with influenza, doing on-the-spot screening with dipsticks; record epidemiologic data such as host, age, and signs/symptoms; and send the samples and information to the laboratory.

Staff at the laboratory would grow, phenotype, genotype, and archive the influenza viruses, taking advantage of high-throughput, automated systems. The plan would improve monitoring of circulating strains, helping researchers, for example, to identify strains that spread from humans to other animals and vice versa. Running full throttle, the laboratory could analyze 100,000 samples per year.

The success of such a program would depend on both physicians and veterinarians. "If a facility like this were turned on, it would depend on what people would be able to provide," said Dr. Layne, a major proponent of the idea. "If [veterinarians] think this is important and want to contribute, they are really in the driver's seat."

The global influenza laboratory has the support of scientists at the national Centers for Disease Control and Prevention, WHO, Armed Forces Institute of Pathology, National Institutes of Health, and USDA.

A pedestrian virus
The flu virus is a small, 13.6-kilobase organism, but it remains shrouded in mystery. Currently, the WHO influenza program involves 111 national centers in 83 countries, and researchers analyze only a small section of the virus when they collect samples.

The virus is tricky because of shifts and drifts in its genome. In the process of drift, small mutations occur in the virus's genes that change the way proteins look to the immune system. In the process of shift, two flu viruses infect the same cell and swap whole segments of one or two genes, resulting in a new strain. This may be how a 1957 strain that killed 70,000 people originated—the strain carried three gene segments from ducks and five from humans.

"Relatively speaking, the human genome is large and quiet, the flu genome is small but very noisy, and we don't know what that noise means," Dr. Layne explained.

We don't know why certain strains are more virulent than others, how the influenza virus genes work together to make a strain virulent or nonvirulent, and why some viruses can spread via aerosol and others can't. "You think that flu is a pretty pedestrian pathogen, but yet, we virtually know little about it," Dr. Layne mused.

The zoonotic nature of certain flu strains adds to the virus's unpredictability. Little is known about the pathogen in wild animals and birds, or about the interaction between infected wild creatures and domesticated animals or humans. "If we are ever going to have a view of any of this, you have to look at the whole picture," Dr. Layne said.

This means that more emphasis needs to be placed on animal strains. "Monitoring animal strains is important, and we should do more in this area," said Nancy Cox, PhD, director, WHO collaborating Center on Influenza at the CDC.

Avoiding a pandemic
A global laboratory would allow researchers to analyze more of the virus genome, in addition to analyzing a greater number of viruses. Scientists hope that by analyzing thousands of viruses, patterns will emerge that will help answer questions, such as why certain strains spread in animals but not in humans, and which human and animal strains crossbreed over time.

If this were successful, other global laboratories might spring up, such as ones for anthrax, HIV, multi-drug-resistant tuberculosis, and foot-and-mouth disease and other diseases that affect food safety.

Currently, however, influenza is the priority, and researchers argue that perhaps the first high-throughput laboratory, and those that follow, will help them to mitigate pandemics such as the one in 1918. In that year, the flu killed an estimated 20 million to 40 million people.

"Around the world, this whole mix of flu is going between humans, domesticated animals, and wild birds," Dr. Layne said. "If something is coming our way, we really have no way of knowing it. It is kind of like the rain. It might rain today, it might rain tomorrow, but when is it going to rain?"