Three Emory scientists have signed a letter published last week in Nature and Science outlining proposed research on the H7N9 avian influenza virus. A strain of H7N9 transmitted from poultry to humans was responsible for 43 deaths in China earlier this year, but so far, evidence shows that the virus does not transmit easily from human to human.
The letter advocates additional research including “gain-of-function†experiments: identifying what changes to naturally occurring viral strains would make them more transmissible, deadly, or drug-resistant in mammals.
The group of 23 flu researchers, led by Ron Fouchier at http://www.agfluide.com Erasmus Medical Center in the Netherlands and Yoshihiro Kawaoka at the University of Wisconsin, say these types of experiments are needed to help public health authorities prepare for and respond to potential future outbreaks.
The letter signers from Emory are: Walter Orenstein, MD, professor of medicine and principal investigator for the Emory-University of Georgia Influenza Pathogenesis and Immunology Research Center (IPIRC), Richard Compans, PhD, professor of microbiology and immunology and scientific director of IPIRC, and John Steel, PhD, assistant professor of microbiology and immunology.
The Emory-UGA IPIRC is one of five flu research centers funded by the National Institute of Allergy and Infectious Diseases.
The flu researchers say the letter was meant to address concerns that previously arose over research on H5N1, another subtype of influenza virus that causes disease in birds and potentially humans.
“With H5N1, we were criticized for not being transparent,” Fouchier told Science. “So this time we want to be sure the public understands what we want to do before we do it, why we need to do it, and how we are going to do it safely.”
Critics have said that gain-of-function cheap oakleys experiments involving avian influenza viruses are potentially dangerous to public health if transmissible virus escaped from research facilities, and also that publication of the results could be dangerous.
Emory’s Walter Orenstein explained the rationale for gain-of-function experiments in an interview with Discovery News:
Instead of being forced to wait and see how many people die during a flu outbreak, scientists would already know which genetic changes make a given flu dangerous. That would make vaccine production a lot easier — and even allow them to pre-empt a deadly outbreak, if they saw certain mutations.
Without that information, health authorities can only react to flu outbreaks, losing lives in the time it takes to develop a vaccine or anti-viral drug. “It takes six months to get a vaccine in gear,” Orenstein said. “With ‘gain of function’ studies, we can determine what it would take to make a flu dangerous; we could make a vaccine and store it.”
…Since the changes in the virus that make it deadly are so specific, only researchers with the unique knowledge acquired from gain of function experiments would likely understand how to counter it. And that would lead to quick development of an antiviral agent or a vaccine. “If Dr. Evil did something like that, we’d be ahead of the game,” Orenstein said.
“Given the unpredictable nature of influenza virus, the short-term benefits obtained from gain-of-function research are difficult to measure,†Steel says. “Still, a benefit of this research is that it would allow scientists to watch out for equivalent changes in natural viruses. This type of monitoring could give public health officials time to prepare vaccines and medicines to protect the human population.â€
“The basic research proposed also has intrinsic value when considered as part of an ongoing, incremental increase in our knowledge of this dangerous pathogen,” Steel says. “Every cheap oakleys experimental result adds one more piece to the jigsaw puzzle. The value of basic science often becomes more apparent over a time frame longer than a couple years, but this does not make it less societally valuable.â€
The flu researchers’ letter, and a supplement detailing regulatory requirements, stresses that all proposed research involving H7N9 must be reviewed by institutional biosafety committees. Separately, any proposed experiments that could generate H7N9 viruses that are more transmissible between mammals must be reviewed by a federal panel.
Emory investigators plan research that includes:
- testing the susceptibility of H7N9 viruses to antiviral drugs
- testing neutralizing antibodies for their ability to counteract H7N9 virus
- probing properties of H7N9 versions of viral proteins (hemagglutinin) that are responsible for entering cells
Some of the proposed research involving H7N9 can take place using inactivated virus or isolated viral proteins. All research involving live H7N9 virus must be performed in a biosafety level 3+ laboratory or for animal research, BSL3-Ag facility. Protective measures in those labs include requirements for protective clothing such as goggles, gloves and respiratory masks, and maintenance of constant negative air pressure.
To perform experiments that require BSL3+ facilities, Emory researchers will collaborate with investigators at the University of Georgia (part of IPIRC) or the Centers for Disease Control and Prevention.
So far, transmission of the H7N9 virus to humans appears to be originating mostly in birds. Chinese authorities closed live poultry markets this spring in response to the outbreak, and these measures seem to have been effective in containing it.
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