GM chicken - a solution to bird flu?

Dr. Ricarda A. Steinbrecher & Dr. Susanne Gura

January 2011

Suppression of Avian Influenza Transmission in Genetically Modified Chickens
Lyall et al. 2011; Science 331: 223-226; DOI: 10.1126/science.1198020; paid-for-access 15$/24 hrs.
Abstract: Infection of chickens with avian influenza virus poses a global threat to both poultry production and human health that is not adequately controlled by vaccination or by biosecurity measures. A novel alternative strategy is to develop chickens that are genetically resistant to infection. We generated transgenic chickens expressing a short-hairpin RNA designed to function as a decoy that inhibits and blocks influenza virus polymerase and hence interferes with virus propagation. Susceptibility to primary challenge with highly pathogenic avian influenza virus and onward transmission dynamics were determined. Although the transgenic birds succumbed to the initial experimental challenge, onward transmission to both transgenic and nontransgenic birds was prevented.

On 14 January 2011, Science published an article by Lyall et al. entitled 'Suppression of Avian Influenza Transmission in Genetically Modified Chickens'. The authors state themselves that their research and results are about a 'proof of principle' - something which by definition is a long way away from actual applicability and does not consider any safety issues.

The ‘proof-of-principle’ claimed is “that genetic modification can be used to prevent avian influenza infection in chickens”. Genetically engineering chicken with a so-called decoy element, Lyall and colleagues can show in experimental setting that whilst influenza infected GM chicken will get sick and die they will not transmit the disease to other chicken, whether these are GM as well or not. The authors also state, that “the specific mechanism underlying this effect is not known.” The decoy itself was first described by Luo et al. in 1997,1 who designed the decoy molecule to resemble an artificial binding site for the polymerase enzyme of the influenza virus. This viral enzyme is crucial for the replication of the virus within the host organism, and if the viral polymerase binds to the decoy it can no longer fulfill its tasks sufficiently.
Yet viruses will still replicate in the infected chicken, though for reasons speculated on but not understood, they can no longer efficiently infect other chicken.

Realities of bird flu and chicken farming

  • Avian Influenza A viruses are widespread in the animal kingdom and consisting of some 144 possible subtypes. 2
  • Birds can be hosts for all known subtypes of influenza A viruses, particular the low pathogenic strains.
  • Low pathogenicity or virulence of subtypes in wild birds is seen as the consequence of a long co-evolution between birds and the influenza viruses, allowing the viruses to remain in their hosts without destroying them.
  • Upon infection, wild birds typically will not get sick. This is also partially the case for some local poultry breeds, which are still prevalent in the Global South, which may carry or be in contact with bird flu viruses but not get seriously sick or die from it.
  • Hybrid chickens and inbred lines, however, easily get sick. Intensive factory farming requires expensive biosecurity measures to protect them from the infections, which are facilitated by factory farming in the first place.
  • The immune systems of these factory farm breeds and hybrids often respond less well to challenges due to a number of factors. These include:
    - reduced genetic diversity (which is crucial for immune responses on the population level), and non-selection in breeds (e.g. Pinard et al. (1991)
    - too much protection e.g. from exposure to germs and thus lack of training of immune system (due to the biosecurity measures),
    - stress (e.g. overcrowded living conditions, see below).
  • Due to their flock size, the living conditions of the chickens and the narrow range and uniformity of the breeds used, huge losses can easily occur, if a factory farm is infected. The whole population will need replacing, often referred to as “depop-repop” by industry experts.
  • The pathogenicity of a virus (such as the speed and ability to infect and kill) can easily increase under favorable conditions. High animal population density is a major contributing factor to the development of viruses from low pathogenicity to high pathogenicity, such as the H5N1 avian influenza virus. “When bird densities are low, a very virulent subtype leading to high host mortality may disappear because of the impossibility of transmitting quickly to healthy birds before the death of sick ones.” (Gauthier-Clerc et al. 2007). In European broiler farms the average density is 22 animals per square metre. The birds can not exercise their natural movements. The air is highly loaded with dust and pathogens. A considerable percentage of animals die before reaching the slaughter weight, indicating their poor health status.
  • Only some 30 breeding lines of broiler and layer chicken are used in chicken factory farming globally. Broiler genetics are provided by only four internationally operating livestock genetic companies; only two of them share the global market for layer hen genetics.
  • Farmers in the South are increasingly outcompeted by huge factory farms owned by large investors. Patents on GM poultry could increase the cost of day old chicken and contribute further to industrial concentration and loss of livelihoods. This is comparable with the higher costs to farmers of GM seed.

Some tragic consequences of avian flu responses

  • Thousands of wild birds were culled before it became clear that the disease travelled along the trade routes of farmed chickens rather than along the migratory routes of wild birds. (see below).
  • Millions of local poultry were culled before it became clear that bird flu was spread by factory farms.

Facts and Figures

  • In September 2006 the World Bank estimated the potential costs of a severe avian influenza (bird flu) pandemic in humans globally to be US$ 2 trillion. This would represent a cut of more than 3 percent of the global economy’s gross national product due to its impact on trade and economic activity (FAO AIDE news 3 and Asian Economic News 4.
  • Over 250 million domestic birds were culled by 2007 in connection with bird flu (S. Cointreau, World Bank 2007: Livestock Interjurisdictional and Intersectoral Issues)5.
  • The costs of the epidemics is not only monetary. Victims are also the priceless diversity of local breeds and specific races. In the Netherlands alone, more than 20 million birds were culled, including rare breeds, as a preventive measure. Lack of understanding, misconceptions, misrepresentations and the interests behind factory farmed poultry have resulted in eradication of local breeds. In many developing countries bird flu was used as an excuse to eliminate local breeds. Once lost these cannot be reproduced easily. Industrial poultry is now understood by many to be at the heart of the epidemic of bird flu. To continue pointing at local breeds and free range production and attempting to curtail these is not only ill advised but will most likely worsen the situation. (Grain 2006: Fowl play)6.
  • In March of 2007 scientific proof was published in the British Ornithologists’ Union journal Ibis, that bird flu did not follow the routes of migratory birds, but rather the routes of poultry trade, both legal and illegal (Gauthier-Clerc et al. 2007).7 A summery of this science paper and additional commentary is provided by Birdlife International 8.
  • After hundreds of thousands of birds had been culled, FAO concluded from a study that contrary to expectations, the small farmers' poultry in Thailand (so-called back yard flocks) had the lowest risk of infection (measured by incidence of detected infection) as compared to in commercial layer and broiler flocks.9
  • The report ‘The Role of the Intensive Poultry Production Industry in the Spread of Avian Influenza’ by Compassion in World Farming (February 2007) adds to the evidence that the development of highly pathogenic strains of bird flu is a direct consequence of factory farming: "Selecting generation after generation of birds for their faster growth rates and higher meat yields has left the birds' immune systems less able to cope with infections and there is a high degree of genetic uniformity in the population, making spread of the virus all the more easy." The report further summarises: "An intensive poultry farm provides the optimum conditions for viral mutation and transmission - thousands of birds crowded together in a closed, warm and dusty environment is highly conducive to the transmission of a contagious disease."10

Addressing the research in question: the GM approach and transgenic chickens

When applying genetic modification technology (GM) it is important to find out whether the modification and the ensuing trait is stable and durable and also whether it has direct or indirect negative side effects and consequences, none of which is known so far.

  • Gene Silencing - if and when gene silencing occurs, the GM trait is not reliable: Organisms have the ability to switch genes or gene sequences off. This is thought to be in part a defence mechanism against ‘intruders’ (e.g. viral sequences), an adaptation mechanism or at times a gene regulation mechanism. Such gene silencing has repeatedly been observed for example in GM plants and their GM traits/genes, especially when introduced sequences are doubled up or repeat already existing sequences (e.g. as in the promoter sequence in the case of the chickens). Whilst gene silencing is also being observed in GM animal systems, this is largely found in situations with genetically modifying somatic cells (body cells) rather then germ line (reproductive) cells.
    Another trigger for gene silencing can be stress, of which chickens will experience a great deal in intensive factory farming conditions. There is still insufficient knowledge about all the different mechanisms involved in gene silencing stimulated by environmental cues. Only long-term studies over many generations and under different conditions can offer any further clues and information on such concerns and risks.
  • Adaptive responses by viruses: Furthermore, viruses are amongst the most adaptive organisms on the planet, constantly out-manoeuvring and overcoming defence mechanisms. The fact that the current polymerase binding sequence is a highly conserved region (stable over a considerable period of evolutionary time) across all influenza A sub-types might be due to the fact that host organisms (e.g. chickens) have not yet found a way to counter it. Genetic engineering presents a new challenge to and pressure on viruses, and we should be ready for them to find ways – perhaps rather novel or unexpected ways - to circumvent our strategies in the not too long term.
  • Risks & negative and harmful side effects: The paper is not dealing with this issue at all. As an attempt to provide a proof of principle the authors do not touch any other concerns, such as risks to health (to either chicken or humans) or environment, biodiversity, livelihoods, food security. It is known though in general, that genetic engineering in itself as well as the addition of new genetic sequences and traits result in unintended and unexpected changes and consequences (for example see EcoNexus paper on Genome Scrambling).
  • The muted virus – an uneasy risk. The virus produced by the GM chicken has to be regarded as a risk in itself. Though the virus produced by the GM chicken seems to be the same virus as before, yet, for unexplainable reasons, it no longer seems to be infective to chicken. It is not clear, what has changed, it is equally not clear, what this change might mean in terms of altered host range, altered pathogenicity, or latency. And if it is no threat yet, it may mutate into one over not too long a time period, given its adaptive potential.

Should this application of GE technology be intended for further development towards actual application to chickens, many long term studies would be required, including investigating whether the chickens might in turn have become more susceptible to other pathogens (including other viruses) and stresses, whether there are alterations in behaviour, nutritional value, growth parameters, etc.. Long term studies would also have to cover the effect on the virus, and the altered behaviour of the virus. In view of the fact that viruses have plainly adapted over time to infect new species, we have to be certain that genetic modification does not stimulate or force the virus to adapt so as to infect different species more readily, including humans.

Conclusion

The real causes for the emergence of highly pathogenic bird flu viruses such as H5N1 strains, and their spread are found in the current practices of factory farming and global trade in poultry. High chicken density for example is key contributor to the development of such highly pathogenic viruses, aided by other factors like untrained immune systems due to high biosecurity measures and genetic uniformity of poultry. A GM approach cannot offer a solution to these problems but might instead unintentionally add to them. In depth deliberations and rethinking are required.