PHOCUS

Proposed implementation

Introduction

For applying PHOCUS in the real world, it is important to also identify potential hazards, risks and other latent barriers that might hinder implementation. Therefore, we have identified our end-users, designed a method for application and determined strategies to mitigate potential risks. A graphical representation can be seen in Figure 1.

Figure 1. A graphical representation of the different components of our proposed implementation of PHOCUS.

End-users

Regular pest control often relies on farmers applying pesticides themselves. Locust control works differently, because of the following reasons; firstly, locust swarms originate from remote and unpopulated areas. Letting them breed unchecked can lead to upsurges, like the current situation. During this breeding phase is the most effective time to intervene and prevent swarms. Secondly, when giant and quick moving swarms have formed, a lot of pesticide needs to be sprayed over vast areas. The scale and costs of both operations is outside the grasp of a single farmer. For these reasons the Food and Agriculture Organisation (FAO) of the United Nations and national governments are the acting authorities on locust control. Therefore, our main end-users are trained professionals from the FAO and national governments.

The FAO is highly involved in the monitoring and control of locust populations [1]. The FAO takes responsibility to purchase and deliver items such as pesticides, equipment, vehicles, etc. to areas of need [2]. They also provide training to locals to properly use these tools and products. From our meeting with members of the FAO we gathered that currently there are two types of pesticides being used. Chemical pesticides, which are quick acting but nonspecific and harmful to other insects and humans, or biopesticides, which are specific but too slow acting. We concluded that there is a need for a product that is fast and safe to replace current options. The FAO is a potential buyer. If they choose to do so, they will ensure that it is properly established, as most member states follow their advice on this matter. PHOCUS could also be bought and used by countries that are financially stable and don’t rely on the aid of the FAO for locust control.

Application

PHOCUS will be applied in the same standardised way as current pesticides used against locusts: by spraying on vegetation in ultra-low volumes using planes, helicopters and cars in which 1 L of PHOCUS is required to spray 1 hectare of land [FAO, personal interview]. In smaller or populated areas, individuals can spray the pesticides on the vegetation in areas that are forecast to be affected. In the larger or more remote areas, preferably planes or helicopters will be used to apply the biopesticide. Simonis B.V. informed us that helicopters are a preferred method of application compared to planes because the air flow created by the rotation of the blades pushes the pesticides down towards the vegetation. Application of PHOCUS will mainly be coordinated by the FAO, as is the situation during the 2020 desert locust upsurge.

Safety considerations

Logistic factors as described above are not the only aspects to consider regarding the implementation of our biopesticide. PHOCUS can influence its environment in a multitude of ways. To anticipate this, multiple safety measures were taken throughout the project. In general the biosafety measures taken consist of:

Non-pathogenicity and non-toxicity of the chosen bacteriophage, target bacteria and the heterologously expressed proteins to any other beings than the desert locust.
Choosing the Cry7Ca1 toxin and the double-stranded RNA molecules, used for RNA interference, that are specific to the desert locust.
Using an encapsulation method, a physical barrier between the phage and the bacteria when first applied on vegetation, to prevent PHOCUS from being active when it is not intended to be.
Combining two different killing methods to prevent the locusts from becoming resistant to the pesticide.
Using multiple phages that target two or three different receptors on the same bacterium, to prevent bacterial resistance from impeding efficacy.

In terms of legislation and procedural safety, we mapped out the EU regulations, which are often seen as a high standard by other countries, and with which PHOCUS has to comply. From this information, we deduced which safety tests must be done so PHOCUS can move from the lab to Field trials. For a full description of all biosafety measures, see Safety.

Safety during manufacturing of PHOCUS should be compliant with the EU standard of Good Manufacturing Practice (GMP). We chose to produce PHOCUS in the EU, because the standard of quality is generally of the highest level, therefore ensuring quality of both the product and production will be easier. For a detailed overview of manufacturing compliance, please see Entrepreneurship > Product.

As discussed previously, PHOCUS will be applied in accordance with the contemporary standards set by the FAO. According to FAO protocol, only trained professionals apply the pesticides, which establishes safe application practices. Due to the similarity in application to current pesticides, we have reason to believe that spraying of PHOCUS will require minimal additional training. As we expect PHOCUS to be safe to humans, exposure to humans should not affect their health. This is in contrast with current chemical pesticides, which require protective equipment to be used. The use of PHOCUS could lift the burden of requiring protective equipment. Although we refrain from abolishing this practice from the start, as the product we are going to implement is biologically and technically complex and there might be unanticipated consequences.

Hurdles

Apart from the socio-technical complexity of our product there are also considerable ethical issues that need to be taken into account. To debate the potential issues of releasing a Genetically Modified (GM) phage into nature, different types of stakeholders should be involved. It can be difficult to come into contact with certain groups. For example, we have run into this problem with NGOs advocating against GM and getting into direct contact with local farmers. Therefore we have described how we set up and maintained contact with a broad range stakeholders to aid others with this. Conducting a discussion is another challenge, since people need to understand what is going to happen and the consequences thereof. The complexity of our project can make this rather difficult. In our project, a big hurdle in this discussion turned out to be the general association of viruses with disease by many people as they have been scared of viruses their whole life, only supported by the recent Covid-19 pandemic. Another hurdle is the acceptance of performing genetic modifications considering that many already advocate against such practices. Again, this issue should be discussed with a broad range of stakeholders, taking the engagement, communication and outreach surrounding the release of gene-drive mosquitoes as an example [2]. To contribute to this we have actively integrated stakeholder opinions throughout our project, as well as enabled the discussion with civil society.

Another hurdle for implementing PHOCUS is legislation. Currently, bacteriophage based technologies have found a resurgence in modern science, from biocontrol to medicine. This quick resurgence has accentuated an inherent problem of radical innovations, the "Pacing Problem" [5]. This describes a situation where policy is lagging behind the frontier of innovation. While this problem is applicable to a variety of technologies, this is also the case for bacteriophages. From an interviewee, Dr. Cécile van der Vlugt, we learned that the best way to deal with this, is by generating data for a risk assessment.

Apart from ethical, social and legislative hindrances, PHOCUS has to overcome technical and physical hurdles. Firstly, bacteriophages are unstable in high UV environments [4], while high UV radiation is a staple of the areas where desert locusts tend to breed. Our proposed usage of encapsulation could alleviate this. Secondly, bacteriophages are often stored in low temperatures as their stability is influenced by temperature [3]. Through interviews with experts, we learned that often, the coolboxes brought by locust control agents are no cooler than 20 °C. No current strategy has been identified to overcome this hurdle, hence more research should be done in this field to improve the implementation of PHOCUS.

Conclusion

The FAO and national governments have been identified as the end-users of PHOCUS. By designing PHOCUS to be compatible with the current FAO standards used for pesticide application against locusts, current methods and practices can remain intact. This results in an easy and safe transition from the contemporary methods to PHOCUS. A multitude of safety measures have been taken throughout the design of PHOCUS, so that hazards are kept to minimum. To aid successful implementation of PHOCUS, potential hurdles have been identified in ethical, social, legislative and technical fields. These are important aspects that require further research, development and execution in order to further improve the implementation of PHOCUS.

References

Page 3 of http://www.fao.org/locusts/response-overview-dashboard/en//
James, S., Collins, F. H., Welkhoff, P. A., Emerson, C., Godfray, H. C. J., Gottlieb, M., Greenwood, B., Lindsay, S. W., Mbogo, C. M., Okumu, F. O., Quemada, H., Savadogo, M., Singh, J. A., Tountas, K. H., & Touré, Y. T. (2018). Pathway to Deployment of Gene Drive Mosquitoes as a Potential Biocontrol Tool for Elimination of Malaria in Sub-Saharan Africa: Recommendations of a Scientific Working Group †. The American Journal of Tropical Medicine and Hygiene, 98(6_Suppl), 1–49. https://doi.org/10.4269/ajtmh.18-0083
Jończyk, E., Kłak, M., Międzybrodzki, R., & Górski, A. (2011). The influence of external factors on bacteriophages—review. Folia Microbiologica, 56(3), 191–200.
Jones, J. B., Vallad, G. E., Iriarte, F. B., Obradović, A., Wernsing, M. H., Jackson, L. E., Balogh, B., Hong, J. C., & Momol, M. T. (2012). Considerations for using bacteriophages for plant disease control. Bacteriophage, 2(4), e23857.
Marchant, G. E., Allenby, B. R., & Herkert, J. R. (2011). The Growing Gap Between Emerging Technologies and Legal-Ethical Oversight. Springer Publishing.

[1] Page 3 of http://www.fao.org/locusts/response-overview-dashboard/en//

[2] James, S., Collins, F. H., Welkhoff, P. A., Emerson, C., Godfray, H. C. J., Gottlieb, M., Greenwood, B., Lindsay, S. W., Mbogo, C. M., Okumu, F. O., Quemada, H., Savadogo, M., Singh, J. A., Tountas, K. H., & Touré, Y. T. (2018). Pathway to Deployment of Gene Drive Mosquitoes as a Potential Biocontrol Tool for Elimination of Malaria in Sub-Saharan Africa: Recommendations of a Scientific Working Group †. The American Journal of Tropical Medicine and Hygiene, 98(6_Suppl), 1–49. https://doi.org/10.4269/ajtmh.18-0083

[3] Jończyk, E., Kłak, M., Międzybrodzki, R., & Górski, A. (2011). The influence of external factors on bacteriophages—review. Folia Microbiologica, 56(3), 191–200.

[4] Jones, J. B., Vallad, G. E., Iriarte, F. B., Obradović, A., Wernsing, M. H., Jackson, L. E., Balogh, B., Hong, J. C., & Momol, M. T. (2012). Considerations for using bacteriophages for plant disease control. Bacteriophage, 2(4), e23857.

[5] Marchant, G. E., Allenby, B. R., & Herkert, J. R. (2011). The Growing Gap Between Emerging Technologies and Legal-Ethical Oversight. Springer Publishing.