COMMENTARY

Controversy over the H5N1 Supervirus

By Lori Fingerhut

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In January of this year, scientists and government officials called for a 60-day suspension of recent research on one of the big shots of influenza viruses, H5N1. At the Erasmus Medical Center in Rotterdam, Netherlands, and the University of Wisconsin – Madison, researchers have succeeded in engineering an H5N1 avian influenza virus that has the ability to transfer from one human to another. H5N1 is a virus that normally affects birds, and transfers to humans only through human contact with infected poultry. With the ability to pass from human to human, H5N1 has the potential to cause a pandemic comparable to the flu pandemic of 1918 caused by the ‘Spanish influenza,’ which killed up to 50 million people in a matter of 3 months. 1 Many scientists argue the research has important public health benefits and needs to be published so that scientists and public health officials can start watching and planning for a potential outbreak. Controversy now exists among the United States and worldwide governments and scientists, however, over whether research should be published on a disease that could kill millions if accidentally or intentionally released.

WHAT IS THE AVIAN FLU?

The avian, or bird, flu is a very common influenza virus among poultry but also has the potential to cross species barriers and infect humans. The H5N1 strain, a highly pathogenic type of avian influenza, is the star of the debate around the current research. After first appearing in humans in Hong Kong in 1997, H5N1 re-emerged in 2003-2004 but was more widespread, impacting countries in Europe, Asia, and Africa. Since then, there have been about 600 reported cases of H5N1 in humans, 60% of which resulted in death. There is currently no evidence that properly prepared meat carries a risk of disease transmission from bird to human. However, eating or handling raw meat at any step in the production line comes with risks for contracting the virus. The ease with which infected birds are transported from country to country increases the public health concerns for humans regarding H5N1. Influenza viruses are known to mutate, and a mutation in the H5N1 virus can turn the virus from one that only spreads to humans by direct contact with infected poultry to one that can spread easily between human beings. If this should happen, the threat of a deadly pandemic increases dramatically. 2

Currently, the exact mechanisms by which the H5N1 virus infects human beings are still unclear. Research has been done to determine how the host’s immune system reacts to the virus and why the virus is so destructive once in the body. Recent research has indicated that progression of disease symptoms may be caused by a large, abnormal immune response, primarily affecting the respiratory system. The H5N1 virus, unlike seasonal flu viruses, can also spread beyond the respiratory tract, though respiratory effects are the most severe and the main cause of human death. Once inside the body, H5N1 damages cells in the lungs, often causing viral pneumonia. 3

THE RESEARCH AND THE CONTROVERSY

As of now, H5N1 has not demonstrated a natural ability to pass from human to human directly. But that may be about to change. Research led by Dr. Ron Fouchier of at the Erasmus Medical Center in the Netherlands and Dr. Yoshihiro Kawaoka of the University of Wisconsin – Madison has led to the creation of a brand new H5N1 virus that has the potential to pass from one ferret to another ferret in the lab. This is significant as the ferret respiratory system bears much similarity to the human respiratory system, making the ferret the perfect animal model for flu research. High-dose exposure to the virus caused the death of both ferrets given the virus directly and those placed nearby the virus. 4 Even more significant was the fact that it took just five mutations for Dr. Fouchier and his team to turn the non- human transmittable H5N1 virus to one that was not only able to spread between ferrets (and thus potentially humans) but was also airborne. 5

Dr. Fouchier’s findings have created a stir in the public health world. On the one hand, understanding the structure and virology of pandemic influenza is the first step in figuring out how to combat it. By finding the mutations that would allow H5N1 to become a virus that can transfer among humans, scientists could monitor poultry, looking out for those particular mutations. Dr. Daniel Perez, Professor of Virology at the University of Maryland and Program Director for the USDA supported Avian Influenza Cooperative Agricultural Project, advocates for this type of avian flu research and publication. “The mutations themselves are not unique or exclusive to the viruses produced in these two laboratories,” he explains. “Make no mistake, it is likely that these viruses can emerge in the field. The question now is not whether H5N1 viruses can be transmitted by aerosol but when it will happen in nature. 6 What ramifications would withholding publication of the material have on public health efforts? Perez asserts, “Preventing access to crucial pieces of information will hamper our ability to develop better vaccines and antivirals against these viruses.” 7

The creation of an H5N1 supervirus is not the first controversial discovery that has been made in the last decade. In 2002, scientists from the State University of New York in Stony Brook manufactured the poliovirus using instructions they found online. Three years later, the 1918 influenza virus was sequenced and reconstructed. Reactions to those discoveries were similar to the reactions to the H5N1 research today. Supporters of the research point out that these syntheses were both made by trained scientists and researchers. At the end of the day, “these are not easy viruses to reconstruct,” says Dr. Diane Griffin, Professor at Johns Hopkins University’s Bloomberg School of Public Health. 8 She argues that synthesizing deadly viruses is not something the average person could do; thus, the potential public health benefits outweigh those risks.

Nevertheless, it is hard to unquestionably accept these arguments when the 1918 influenza virus, which killed over 50 million people, had a mortality rate of approximately 2.5% while the current H5N1 virus is alleged to have a mortality rate close to 60%. “I don’t like to scare people,” says Paul Keim, microbiologist and chair of the US National Science Advisory Board for Biosecurity (NSABB), “but the worst-case scenarios here are just enormous.” 9 Keim argues the stakes are much higher with the new H5N1 virus than they were with even the 1918 influenza virus. Given that the virus spread to nearby ferrets in the lab, scientists and policy makers fear that the newly created H5N1 virus would be a double whammy, combining the mortality of the 1918 virus with the ease of transmission of the average seasonal flu. In short, the researchers turned a potentially deadly influenza virus into a cold killer. In addition, as University of Florida – Gainesville microbiologist Kenneth Berns explains, there are no vaccines or drugs known to be effective against this synthesized H5N1, which also greatly increases the risk of the virus. 10

Perhaps the greatest concern of those against publication of this research is the possibility that the mutated H5N1 virus could be used purposely as a bioweapon, leading them to believe the research should be censored. “In nuclear physics,” says Dr. Selgelid, director of the Center for Human Bioethics at the Monash University in Melbourne, Australia, “discoveries with weapons implications are automatically born classified in the United States whether or not the research is funded by governments. This study,” he continues, “reveals that biological sciences are now in a situation similar to that of atomic physics.” 11

CONCLUSION

For the time being, only pieces of Dr. Fouchier and Dr. Kawaoka’s research findings have been published. On February 17, 2012, it was announced that the research would eventually be published in full. 12 Since then, Dr. Fouchier has done his fair share to assure the world that the dangers of his findings and the implications of his research are being exaggerated. The strain he created, he claims, was not as lethal or as easily spread as reported. 13 Regardless of when the study is published and what details are included, the debate has placed a new light on the freedom of biological research in the eye of biosecurity.

REFERENCES

1. “Planning for Avian Influenza.” Annals of Internal Medicine. American College of Physicians. <http://www.annals.org/content/145/2/141.full>
2. “Avian Influenza.” WHO: Avian Influenza. World Health Organization. <http://www.who.int/mediacentre/factsheets/avian_influenza/en/>
3. Peiris, Joseph Sriyal M., Chung Y. Cheung, Connie Yin H. Leung, and John M. Nicholls. “Innate Immune Responses to Influenza A H5N1: Friend or Foe?” Trends in Immunology 30.12 (2009): 574-84.
4. Kofman, Jeffrey. “Researchers Pause Work on Bird Flu That Could Kill Hundreds of Millions.” ABC News 20 Jan. 2012. <http://abcnews.go.com/Health/inside-lab-scientists-created-deadly-bird-flu-virus/story?id=15371697#.T1q3Wo4zJ_n>
5. Butler, Declan. “Caution Urged for Mutant H5N1 Avian Flu Work: Scientific American.” Scientific American. Nature Magazine, 25 Jan. 2012. <http://www.scientificamerican.com/article.cfm?id=caution-urged-for-mutant-h5n1>
6. Perez, Daniel R. “H5N1 Debates: Hung Up on the Wrong Questions.” Science Magazine 335.6070: 799-801. American Association for the Advancement of Science, 19 Jan. 2012. <http://www.sciencemag.org/content/335/6070/799.full>.
7. ibid
8. Kwek, Glenda. “Armageddon Super Virus Recipe: Keep Secret or Publish?” The Sydney Morning Herald. 6 Dec. 2011. <http://www.smh.com.au/technology/sci-tech/armageddon-super-virus-recipe-keep-secret-or-publish-20111206-1og76.html>.
9. Ledford, Heidi. “Call to Censor Flu Studies Draws Fire.” Nature Publishing Group, 3 Jan. 2012. <http://www.nature.com/news/call-to-censor-flu-studies-draws-fire-1.9729>.
10. ibid
11. Kwek, “Armageddon Super Virus Recipe: Keep Secret or Publish?”.
12. Grady, Denise. “Despite Safety Worries, Work on Deadly Flu to Be Released.” The New York Times, 17 Feb. 2012. <http://www.nytimes.com/2012/02/18/health/details-of-bird-flu-research-will-be-released.html?_r=1&scp=2&sq=H5N1&st=cse>.
13. Park, Alice. “Dangers of Man-Made Bird Flu Are Exaggerated, Its Creators Say.” TIME: Healthland. TIME, 2 Mar. 2012. <http://healthland.time.com/2012/03/02/dangers-of-man-made-bird-flu-are-exaggerated-its-creators-say/>.


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