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September 26, 2013 | By:  Julia Paoli
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Mutated Avian Flu Virus Causes Controversy

For much of human history science has ignited controversy. Whether the cause is a radical new concept or invention, scientific curiosity is often followed by uproar. Now, two studies about the feared H5N1 virus have ignited a whirlwind of debates and attracted a lot of media attention. At the core of the matter is a mutated avian flu strain of H5N1 that the scientists created. This super strain has caused the global community to reconsider the balance between scientific research and citizen's safety.

H5N1 is a type of avian flu virus that occurs naturally in various types of birds but has surfaced in humans in the last ten years. Although human cases of H5N1 are rare, the virus has a 60% mortality rate. Approximately 600 cases in humans have been reported so far - mostly in Asian countries. Luckily, H5N1 doesn't transmit easily between people. Almost all reported cases are due to direct or close contact with infected birds. Odds are it's only a matter of time until H5N1 becomes readily transmissible. Influenza viruses are known to jump from species to species and frequently "undergo genetic changes" that allow them to adapt.

Many infectious disease specialists agree that a major hindrance in the prevention of influenza pandemics is the unknown way in which animal born influenza viruses mutate to become transmissible in humans. Ron Fouchier of Erasmus Medical Center in the Netherlands and Yoshihiro Kawaoka of University of Wisconsin independently set out to discover how H5N1 mutates. They reasoned that it'd be better to tinker with H5N1 in the lab and gain knowledge for its prevention than sit back and wait for mother nature to concoct a human-friendly strain. Both teams of researchers artificially mutated H5N1 to spread easily amongst ferrets. Ferrets are commonly used as stand ins for humans in influenza studies. To clarify what I mean by "easily" spread, at the end of Fouchier's study the strain had gained the ability to transmit through the air- an unprecedented feat!

How on earth could the scientists have possibly created this super strain? Well ... actually I can't tell you because the U.S. Government has censored the studies. Like I said, the papers are controversial. The public and US Government are not too pleased with these two studies. Fears have surfaced that experimentation with such a deadly virus is dangerous and unethical. And it's no surprise; even the scientist Fouchier calls his super strain "one of the most dangerous viruses you can make." A major concern is that H5N1 could escape from the lab. If that were to happen could a pandemic ensue now that a genetically altered, lethal bird flu is running rampant? Adding fire to the flames is the fact that the studies were done in BSL-3 enhanced labs, which are one tier lower than BSL-4 labs, the safest in the world. The US Government is also concerned that publishing these findings could aid terrorists. If the methods for producing the mutated strain got into the wrong hands then, H5N1 could be used as a weapon of mass destruction against humanity. When the teams of researchers went to publish their findings in Science and Nature journals respectively, the U.S. National Science Advisory Board for Biosecurity took an unprecedented step and asked the journals to refrain from publishing the studies' methods. Many find this demand to be out of line. Scientists pride themselves on the ability to share knowledge freely without political pressure. Very rarely has the government ever restricted scientific discoveries in modern history. In their defense, the U.S. National Science Advisory Board for Biosecurity released a statement saying that the malicious release of H5N1 would result in an "unimaginable catastrophe for which the world is currently inadequately prepared." Fouchier, one of the creators of the superstrain, denies that H5N1 is as deadly or contagious as the media has led people to believe. As proof, he has revealed that not all of the healthy ferrets exposed to the coughs and sneezes of sick ferrets became infected, and of those infected none of them died. Nevertheless, the editors of the journals have complied with the government's request of publishing modified versions of the studies without certain key information.

In January 2012, 40 top influenza researchers around the globe, including Fouchier and Kawaoka, agreed to a voluntary 60 day moratorium on their work to allow for discussion on the matter. But these experts did not sit passively. Soon after the moratorium announcement the 40 scientists released a letter in Nature urging for the continuation of research on H5N1. They argue that studies are a necessary preventative measure against a naturally occurring outbreak and will give officials valuable knowledge in a pandemic situation.

The overwhelmingly negative reactions have launched these two studies into the limelight and brought forth debates over other "dual use research ." Dual use research are studies that are potentially hazardous but may yield beneficial knowledge. It is under debate whether the benefits of studying lethal viruses outweigh the potential risks. In the case of H5N1 one side argues that scientific research is crucial to better protect the world from naturally mutated H5N1. The other side argues that these studies are too risky for today's world. The threat of bioterrorism or an accidental release of the virus from the lab are powerful arguments against research. Many question whether it is ethical to expose the public to such risks in the name of science. The US National Institutes of Health held a meeting in December to analyze the pros and cons of continuing with research on mammalian transmissible H5N1. At the meeting it was decided that dual edged studies can continue but under new, stricter regulations that monitor research and assess the risks attached. In addition, the World Health Organization has released biosafety guidelines for H5N1 studies in the hopes of decreasing the likelihood of a lab breach.

Six months after the U.S. National Science Advisory Board for Biosecurity halted the complete publication of the two studies, the board decided to allow the full release of the papers. Not coincidentally, the WHO okayed publication as well.

Now I can finally tell you how exactly the scientists managed their feat of making an air-transmissible H5N1. The uncensored study by Fouchier reveals that the H5N1 super strain underwent five mutations to become transmissible between ferrets through the air. Two of the five mutations are frequently seen in wild strains of H5N1, while a third mutation has been found only once in naturally occurring H5N1. The other two mutations have never been discovered in natural H5N1 but have been identified in strains of H2 and H3 influenza virus. Fouchier took H5N1 and added three mutations to it before exposing the ferrets to the modified strain. As the virus passed through 10 generations of ferrets the remaining two mutations were picked up. Scientists initially passed the virus from one ferret to another by directly exposing one ferret to infected nasal swabs. After the virus had acquired the needed mutations it became airborne. A further study published by Fouchier, Kawaoka, and Derek Smith of the University of Cambridge found that some naturally occurring strains of H5N1 are only three mutations away from reaching the five mutations found in Fouchier's superstrain. Using mathematical formulas, the scientists concluded "the remaining three mutations could evolve in a single human host, making a virus evolving in nature a potentially serious threat." If natural H5N1 were to evolve and acquire all five mutations then the world would have a airborne transmissible virus in humans deadlier than the virus that caused the 1918 Spanish Flu. Despite their risks, Fouchier and Kawaoka's studies are important because they have given the scientific community insight into which mutations to monitor in the wild. Now that researchers know which mutations are needed for mammalian transmission more effective preventative measures can be established.

Let me know what you think of the debates surrounding the two studies on H5N1. Do you think it was right for them to be published in full? Or do they present an unwelcome opportunity for terrorism?

References:

CDC. Avian Flu (2013).

Grady, D. "Genetically Altered Bird Flu Virus Not as Dangerous as Believed, Its Maker Asserts." The New York Times. Febuary 29, 2012.

McNeil Jr., D. "Bird Flu Paper Is Published After Debate." The New York Times. June 21, 2012

Park, A. "Government Panel Defends Censorship of Bird Flu Virus Research." Time. January 31, 2012.

Park, A. "Dangers of Man-Made Bird Flu Are Exaggerated, Its Creators Say." Time. March 2, 2012.

Sifferlin, A. "Scientists Push to Resume Research On Virulent Man-Made Flu Virus." Time. January 23, 2013

Walsh, B. "Should Journals Describe How Scientists Made a Killer Flu?"Time. December 21, 2011

WHO. H5N1 Influenza (2013).

Images:

1. Cynthia Goldsmith (via CDC).

2. Microbe World (via Flickr).




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