Genetically modified influenza viruses scare the world

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© Shutterstock

Some of the most disastrous pandemics which have occurred have been caused by influenza viruses. The apparition of such dangerous strains could be due to some genetic reassortments of avian and human strains like for the Asian (1956) and Hong Kong (1967) flues pandemic or by adaptation of a pure avian strain like the Spanish flu of 1918 which killed up to 50 million people. In addition, the seasonal influenza still kill up to 500 000 people in the world each year. The comprehension of these viruses has thus become an important issue to prevent any new pandemic in an overpopulated global world.

The work of two research teams which have tried to anticipate and to construct the modifications that could lead to a novel and dangerous strain of avian influenza virus had a great resounding in the world, many people were afraid that these works could one day lead to a sanitary disaster or be used by bioterrorists.

Review of the avian influenza virus

The influenza virus is a widespread virus found in many animal species such as humans, dogs, birds, marine mammals, pigs and horses. Wild aquatic birds appear to be the natural reservoir of the avian virus in the nature. These avian viruses can occasionally infect humans, but their transmission remains inefficient. It was thought that the emergence of pandemic in human population could only happen after genetic reassortment between humans and avian strains of influenza. However many cases of direct infection with an avian virus have been more frequently reported these recent years.

The fact that dangerous influenza viruses could acquire an airborne transmission between humans was an important question for the preparation to face a pandemic. This was for this reason that some laboratories have investigated the routes of influenza transmission between mammals and tried to anticipate how they could acquire dangerous properties for humans in a wild evolution

The Yoshihiro Kawaoka team of the University of Wisconsin-Madison has mutated virus surface genes of the H1N1 virus responsible of a pandemic in 2009. They tested their modified virus on ferrets, a mammal that present the same symptoms as human when infected with the human influenza A virus, and identified mutations capable of giving the airborne transmission between ferrets and that could have been acquired in the nature by simple mutations.

These possible mutations have been examined by another team led by the professor Ron Fouchier at the Erasmus Medical Center if Rotterdam (Netherlands). They have worked on an Indonesian strain of A/H5N1 virus isolated in 2005 and have demonstrated that only five mutations were needed the airborn transmission between mammals to the virus

Debate about publishing research

The multiplication of outbreaks and of the transmission cases to humans has raised concerns about a possible influenza pandemic. The worst case would be the emergence of novel strain for which the population would not have immunity combined to an airborne transmission between humans. The global travel could allow the virus to be propagated around the world in a very small time. The preparation of a pandemic has become an important issue as said by Yoshihiro Kawaoka in his paper Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets:

“It is critical that we understand the molecular changes that may viruses transmissible in mammals. Such knowledge would allow us to monitor circulating or newly emerging variants for their pandemic potential, focus eradication efforts on viruses that already have acquired subsets of molecular changes critical for transmission in mammals, stockpile antiviral compounds in regions where such viruses circulate, and initiate vaccine generation and large-scale production before a pandemic”

However, some people were worried about publishing these potentially dangerous researches which could be used by bioterrorists or lead to an accidental release from a lab. These sorts of researches are called dual use researches because they include negative or positives applications. The US National Science Advisory Board for Biosecurity (NSABB) has recommended that the two papers about modified avian influenza virus should be censored. But few months after the NSABB recommended the full publication of the Yoshihiro Kawaoka paper and the publication of the data, methods and conclusion of the second paper by Ron Fouchier. Previously the World Health Organization has recommended the full publication of both papers.

Some scientists have also expressed some concerns about these experiments on the influenza virus, arguing that the predictions of the timing, the evolution and the mutations effects on the virus were very difficult (11). The experiments on virus that could infect and evolve in humans should have a special treatment. One of the propositions made is to limit the number of laboratories allowed to work on the modified strains of influenza virus. Another is to evaluate the skills of the laboratory workers as much as the physical barriers present in a laboratory to give a safety level as accurate as possible. A competent committee should be created to evaluate which laboratory can work on which virus strain. This committee should have also a decision making authority that lacks currently to the NSABB which gives only advices.

Some other scientists like the virologist Vincent Racaniello said that it would be preferable to use the money for the laboratories to develop more drugs against the flu and to find and universal vaccine.

The researchers working on the H5N1 virus chose in January 2012 to observe a voluntary moratorium to be sure that the international community and the public understand well the risks and benefits of such experiments. Many scientists working in the virology field said that the benefits and the knowledge acquired in the paper outweighed the risks decided to respect the concerns that could arise and chose to be the more transparent possible in their research (3). During this pause, governments and international organizations have been reviewing the biosafety of these researches, sometimes creating new policies or regulation as the US government. It remains to be determined which organizations are able to determine if the benefits or some research outweigh the risk for the society. As said by Anthony S. Fauci and Francis S. Collins in their paper Benefits and Risks of Influenza Research: Lessons Learned:

“A social contract among the scientific community, policy-makers, and the general public that builds trust is essential for success of this process.”

William Fontanaud

Sources:

Fouchier RA et al, 22 June 2012, Airborne transmission of influenza A/H5N1 virus between ferrets, Science.;336(6088):1534-41.

Yoshihiro Kawaoka et al, 21 June 2012, Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets, Nature. doi:10.1038/nature10831

Anthony S. Fauci, 09 October 2012, Research on Highly Pathogenic H5N1 Influenza Virus: The Way Forward, mBio doi: 10.1128/​mBio.00359-12

Ron A. M. Fouchier, Adolfo García-Sastre and Yoshihiro Kawaoka, 09 October 2012, The Pause on Avian H5N1 Influenza Virus Transmission Research Should Be Ended, mBio doi: 10.1128/​mBio.00358-12

Ed Yong, 21 June 2012, Second mutant-flu paper published, Nature, doi:10.1038/nature.2012.10875

Nature editorial, 02 May 2012, Publishing risky research, Nature, doi:10.1038/485005a

Anthony S. Fauci and Francis S. Collins, October 26 2012, Benefits and Risks of Influenza Research: Lessons Learned, Sciencemag, 10.1126/science.1224305

Ed Yong, Influenza: Five questions on H5N1, 21 June 2012, Nature, doi:10.1038/486456a