Overview
The activities of iGEM involve presenting synthetic biological solutions to social issues. In undertaking iGEM activities, we need to bring our laboratory work out into the wider world. This is because we must understand whose issues we are addressing, with what technology, and how we are solving them, as well as how the solution will affect whom. Moreover, we must repeatedly engage in trial and error to maximize positive impacts and minimize negative ones.
We realized that the process of an iGEM project closely resembles the process of “innovation.” Innovation is defined as a “new or changed entity, realizing or redistributing value” [1] . In other words, it is the very thing of value that allows someone to obtain something desirable. This differs from simply creating new or improved technology. Whether in the iGEM project or any other endeavor, if we wish to enrich people’s lives with our technology, we must not focus solely on refining the technology. We need to consider what kind of value for whom we are creating with our technology, and how that technology will affect whom (whether positively or negatively).
This process cannot be accomplished overnight. Therefore, it is important to properly manage and operate the process. We decided to refer to methods of innovation management as a way to manage our project. After discussions within the team, we decided to carry out the project based on the “Innovation Management System (IMS)” defined in ISO 56002.
The ISO 56000 series standards are international standards that codify insights collected as best practices of IMS by a committee comprising 72 countries, regions, and international organizations established within ISO (International Organization for Standardization) in 2013[2] . Among them, ISO 56002 is a standard that provides guidance on ISM as an international standard. Based on the IMS defined here, we will conduct our Human Practices after reconsidering it to align with the philosophy and activities of iGEM. IMS comprehensively includes not only the progress of the project but also the principles and philosophies to carry it out, team design, leadership, and progress evaluation, enabling comprehensive management of the iGEM project.
It should be noted here that our IMS differs from the original IMS because it is conducted based on interviews. In the original IMS, the Solution becomes the actual product or service provided, but in the cycle of iGEM, it is extremely difficult to reach the point of implementation in society. Therefore, the Solution will be what is shown in Wet or Dry (not actually deployed in the real world). As we will explain later, Deploy Solution mainly consists of interview and experimental results.
Innovation Management System
IMS is not an international standard for innovation, but an international standard for innovation management. In other words, it is highly useful not in terms of the content of Human Practices, but in how to proceed with Human Practices. This system is divided into three parts: principles, system building within the team, and actual activities. A characteristic of this framework is that it provides guidance not only on the framework for activities but also on what kind of team building should be aimed for.
Principles
The following eight principles are listed as fundamental principles for innovation management:
Realization of value : Continuously pursuing value for society and service beneficiaries
Future-focused leaders : Taking leadership aimed at the future we want to create
Strategic direction : Acting based on reform guidelines for the organization to survive long-term in response to environmental changes
Culture : Placing importance on “creativity” and ensuring psychological safety and diversity within the organization
Exploiting insights : Finding the future from changes in society and creating the future
Managing uncertainty : Evaluating internal risks of activities and continuing to experiment based on that
Adaptability : Responding flexibly with the assumption that things will not go according to plan
Systems approach : Viewing innovation management as a single system
While what we do is “innovation”, it is also Human Practices. Since IMS was originally created for corporate activities, it lacks some principles necessary for iGEM. Therefore, we added the following two principles that are essential for Human Practices:
Responsive : Conducting activities responsibly in accordance with iGEM’s values
Reflective : Incorporating activities through discussions with diverse external actors
System building within the team
As necessary elements for system building, IMS lists “Context of the organization,” “Leadership,” and “Plan.” The explanations for each are as follows. Note that we have struck through management perspectives that are not emphasized in iGEM.
| Elements | Description |
|---|---|
| Context of the organization | • Are we constantly striving to understand the external and internal circumstances surrounding our organization, as well as the needs and expectations of both internal and external stakeholders? • Do we have our own innovation intent and concept, and are we clearly defining the scope of the IMS based on that? • Are we working to build an organizational culture conducive to fostering innovation, and clarifying the manner and purpose of collaboration with external parties? |
| Leadership | • Are we demonstrating a balance between opportunities and risks, indicating our tolerance for failure, and showing commitment to realizing value? • Are we clearly establishing the vision, strategy, and policy for innovation, and disseminating them throughout every corner of the organization? • Are we clearly assigning the roles, responsibilities, and authorities related to innovation, and ensuring they permeate throughout the organization? |
| Plan | • Are we including in our plans the uncertainties and acceptable or unacceptable risks involved in pursuing opportunities? • Are we establishing verifiable innovation goals at each department and hierarchical level? • • Are we establishing and managing our own portfolio of innovation initiatives, and rearranging priorities as necessary? |
Actual activities
As mentioned earlier, we conducted our activities using the Innovation Management System. The system functions as follows.
- Plan
- Planning the schedule for the entire year
- Setting achievement goals
- Do
- Identify opportunities・Create concepts・Validate concepts・Develop solutions・Deploy solutions
- Regarding the deployment of solutions, we have made modifications to suit the iGEM cycle as explained earlier.
Elements Description Identify opportunities • Acquire insights and knowledge about stated and unstated needs and expectations.
• Acquire insights and knowledge about relevant trends and issues.
• Identify and define opportunities or areas where opportunities exist (including their potential impact, possible value realization, or problem descriptions).Create concepts • Create a concept (value realization model) and decide what kind of value to deliver to which customers, what activities are required for that, with whom to collaborate, and how to generate profits.
• Formulate hypotheses about what kind of value to deliver and how, and visualize these hypotheses to be tested in the next “Validate concepts.”Validate concepts • Validate the hypotheses.
• Since the risk that the hypotheses are incorrect cannot be eliminated, reduce it to an acceptable level.Develop solutions • Develop solutions based on concepts where uncertainties have been reduced through prior activities.
• Collaborate with external parties as necessary.Deploy solutions • Deploy the solution.
• Interview about the anticipated impacts when introducing the solution into society.
• Explore new opportunities based on the feedback obtained. - Check
- Performance assessment using Human Practices Matuality Model
- Act
- Strengthening strengths, overcoming weaknesses, and correcting deviations and non-conformities
The above describes a large PDCA (Plan-Do-Check-Act) cycle, but during our actual activities, we rotated the PDCA at a more granular level. Each process of interviews, where we received feedback on our project from people with various backgrounds during the Do phase and reflected upon it, is an example of this. We followed a cycle as outlined below:
Plan: Set what we want to clarify in this section.
Do: Conduct interviews and discussions. We refer to 2023 Mcgill[3] to describe the interviews.
Check: Summarize what was obtained during the Do phase.
Act: Decide what to do in the next section.
We advanced the project within the framework of the methodology described above. However, since this methodology only outlines the broader strokes, we sometimes found ourselves uncertain about how to proceed in specific areas. Whenever we faced such issues, we researched and implemented methodologies to address them. The methodologies related to activities accompanying the IMS are compiled on the Innovation Management page .
Context of the organization
Like other iGEMers, we wanted to use the power of synthetic biology to solve issues in our region (Japan) and ultimately around the world. Below are the aspirations we confirmed when forming our team about what we wanted to achieve in iGEM:
- Solve problems for someone within Japanese society where we live.
- Also address global issues.
- Tackle problem-solving without depriving anyone of their happiness.
Regarding which specific opportunities to focus on for our project, we identified them through brainstorming and interviews with experts, as presented in the next section.
Additionally, to build our team’s structure, we undertook the following:
We realized that innovation requires not only technical expertise but also insights from the humanities and social sciences, as well as knowledge for idea creation. Therefore, we organized brainstorming methods based on humanities and social science classes and compiled them as insights usable in iGEM. We also all read “Issue Driven” by Kazuto Ataka, a famous book in idea creation, as assigned reading.
iGEM projects are filled with various wisdom for solving problems through synthetic biology. To understand the recent developments in iGEM, we divided and thoroughly read the 2023 Wikis and shared the documents within the team.
Leadership
Our team appointed leaders for the team overall, as well as for Wet, Dry, and Human Practices sections. These leaders guide their respective sections. We all clearly agreed on our objectives and confirmed that each section would operate under the leadership of its respective leader.
While it takes time to determine if our project aligns with our goals, it’s important to know as soon as possible to avoid wasted efforts. We set October, when the Grand Jamboree takes place, as our deadline and defined project failure as the inability to create a Proof of Concept (PoC) for our project by then.
Plan
We have confirmed our agreement for the 2024 project as aiming to solve Japanese and global issues in a sustainable manner without compromising the happiness of others. We have also confirmed that we will execute the project with a deadline of October.
We have decided to select an appropriate project theme and confirm its feasibility by October. Here, we will explore and consider the context of the project in relation to diverse people and society, anticipate future positive and negative impacts, conduct appropriate research design, and examine the limitations of the project’s feasibility.
Do
Sec1: Identify opportunities
Plan
We will conduct a brainstorming session to determine what specific target and problem we will address in our project under these goals. After that, we will make a decision on the proposal through literature review.
Do
The first step in solving social issues through synthetic biology is to express all the problems and questions we have about society and delve deeper into those topics. We decided to narrow down issues that could potentially be solved in iGEM by practicing methodically structured brainstorming. For the methodology of brainstorming, please refer to the Innovation Management page .
Through this process, we were able to generate over 100 ideas, ranging from topics related to our daily lives to somewhat extraordinary topics. Below are some examples of ideas that emerged from our brainstorming:
- Issues with rice
- Sleep disorders
- Soil and water pollution
- Allergies
- Dyes
From among these ideas, we decided to conduct more detailed research on five themes. We then decided to choose one of them through internal presentations and discussions with our PI.
We shared the results of our investigations into background information on each theme obtained through brainstorming, as well as the outcomes of our team discussions on detailed information about the systems, through presentations. Each team gave a presentation within five minutes, followed by questions and discussions to determine what each group was considering and whether it was feasible.
Through this process, we concluded that the project on RNA pesticides for rice blast disease among the rice issues and the project on drugs to overcome sleep disorders were worth reconsidering. Both are issues close to us, and finding solutions for these would have a significant impact on both the development of synthetic biology and our lives. We decided to make a final decision through discussions with our PI.
Through discussions with our PI, we assessed whether the project was actually researchable and feasible. After these discussions, we decided to adopt the RNA pesticide project for rice blast disease as our project for this year.
Rice blast disease is one of the three major diseases affecting rice and is rampant worldwide. The main countermeasure against it is chemical pesticides, but alternatives are sought due to issues like resistant strains. Therefore, we decided to implement countermeasures using RNA pesticides.
Check
We have chosen to create an RNA pesticide project targeting rice blast disease as our project for this year. Rice blast is a disease that has a significant impact both globally and in Japan. While research on RNA pesticides for rice blast is progressing, there are no examples of actual implementation yet. We aim to contribute to solving the rice blast problem by creating and improving RNA pesticides.
Act
In the next section, we will create specific concepts to realize RNA pesticides for rice blast disease.
Sec2: Create concepts
Plan
We are concerned about the stability of RNA pesticides for rice blast disease in outdoor environments. We will create a concept to address this issue.
Do
Based on various literature reviews, we discussed several ideas regarding RNA pesticides for rice blast disease. Among them, we came up with the following concept.
To confirm whether this concept is feasible and how to realize it concretely, we decided to interview multiple experts on MV.
Why did we establish contact?
Professor Taguchi and Assistant Professor Koh at Kobe University are researching methods for producing membrane vesicle and are considering encapsulating various substances within MV in their research plans. We spoke with them to confirm whether the concept of encapsulating RNA within MV can be realized.
What we learned
- Although it depends on the concentration of shRNA, it is probably possible to encapsulate RNA within MV .
- RNA decomposes quickly in the air, so experiments need to be conducted carefully.
- It might be worth considering creating RNA with secondary structures other than hairpins.
- Since it would be beneficial if it could both enter the plant for prevention and act on and destroy the fungus, how about considering a method to create MV that mimic the invasion mechanism of oryzae? By implementing surface display of spike proteins to make it behave like oryzae, we could create a vaccine using attenuated oryzae .
Reflection
This interview suggested that the idea of encapsulating RNA within MV is feasible. Additionally, the idea of displaying proteins on the surface emerged during the discussion.
Why did we establish contact?
Professor Matsuura specializes in synthetic biology at Tokyo Institute of Technology. Since his research includes artificially creating membranes and encapsulating RNA within them, we interviewed him. Based on the discussion with Professor Taguchi, we decided to particularly discuss surface display on MV.
What we learned
- Surface display is commonly done in yeast but is tricky in E. coli.
- It’s quite challenging to bring enzymes produced inside E. coli to the outer membrane; we need to carefully check whether the protein is hydrophilic or hydrophobic.
- There is a method to chemically modify enzymes onto the surface of MV afterward (SNAP-tag system ), but the cost is relatively high.
- The concept could also be realized using a system with artificial cells. While legal aspects might be clearer, technical difficulties are likely to be high.
Reflection
It became clear that there are several points to consider regarding methods to display proteins on the surface of MV. Also, since there’s an approach using artificial cells, we realized we should consider that as well.
Why did we establish contact?
Associate Professor Toyofuku researches microbial interactions at the University of Tsukuba and specializes in membrane vesicle. Based on the previous interviews, we asked whether RNA can be encapsulated within MV and whether mass production is possible for practical use as a pesticide.
What we learned
- Although E. coli has a low RNA expression rate, increasing the expression rate makes it possible to encapsulate RNA within MV.
- (Regarding surface display) In applications for plant prevention, since the process scrapes the plant cell wall, the damage might prevent the desired preventive effect, so we need to consider countermeasures. For example, methods that directly target fungi or approaches where the enzyme displayed on the surface itself exhibits antibacterial effects.
- To increase the production of MV, it might be beneficial to inhibit cell wall synthesis with antibiotics.
- Mass production is possible , I believe. We could use signals to localize RNA, but simply increasing the amount of RNA is the quickest method.
- During MV production, it might be easier to lyse E. coli . It would be good to have a circuit that triggers cell destruction when the amount of shRNA reaches its maximum.
Reflection
We confirmed that we can encapsulate RNA within MV and even achieve mass production. However, it also became clear that there are several issues to consider, such as methods for mass production and RNA concentration.
Check
We decided to establish the concept of encapsulating RNA pesticides in MV as the content to be pursued. Through the interviews, we learned that this is theoretically feasible, and additionally, it was revealed that by performing surface display, we may be able to construct a more effective RNA pesticide delivery system.
Act
We must be mindful that these interviews were primarily conducted with MV experts. We need to confirm from a different perspective whether our idea will actually have an impact on solving the rice blast disease problem as a pesticide.
Sec3: Validate concepts
Plan
While we found that our concept was feasible, we needed to confirm what actual impact it would have as an RNA pesticide for rice blast disease. Therefore, we decided to conduct interviews with experts in RNA pesticides.
Do
Why did we establish contact?
Ajinomoto Co., Inc. is one of Japan’s leading companies researching RNA-based pesticides. We reached out to gain insights into their approach and to better understand the current landscape of RNA pesticides.
What we learned
- Ajinomoto utilizes Corynebacterium for RNA production due to its advantages, such as low RNase activity. This microorganism is already used in industrial applications.
- In contrast, Escherichia coli produces lower amounts of RNA. Additionally, the requirement to produce large quantities of MV poses another significant limitation.
- In the case of pesticides, long-chain double-stranded RNA (dsRNA) is often utilized, as short hairpin RNA (shRNA) may be shorter than the effective length for RNA interference.
- Regarding the efficacy of RNA against fungal targets, there is a concern that fungal cells may not readily uptake the RNA due to protective barriers. Therefore, strategies that involve surface display to enhance uptake may offer a promising avenue.
Reflection Our concept addresses the key elements required for targeting fungi; however, challenges related to production efficiency and the mechanism of action may hinder its effectiveness.
Why did we establish contact?
Professor Suzuki is researching pesticides against insects and is well-versed in RNA pesticides. We asked him to tell us about the current state of RNA pesticides and the goals our concept should achieve, to compare it with the reality of our concept.
What we learned
- Research on RNA pesticides is mostly aimed at insects because penetrating bacterial cell membranes is difficult.
- RNA pesticides are significantly cheaper to develop compared to chemical pesticides. The production cost of RNA has also become dramatically cheaper than before, now at $1 per gram. Efficient production like this is being carried out using cell-free systems at GreenLight Biosciences and using Corynebacterium at Ajinomoto.
- In the case of fungi, it is known that longer RNAs (around 600 bases) are more effective, so this will be a key point for rice blast disease as well.
- The mechanism by which RNA is absorbed into leaves is not understood. However, when labeled, it accumulates around stomata and between cells. Incorporating a system for appropriate delivery to target sites is one framework of ideas.
- Resistance to RNA sequences has been known before, but it has also been found that organisms can develop resistance by no longer taking up the RNA itself. It would be beneficial if we could easily address such issues as well.
Reflection
Based on the interview, we realized that our concept can solve the key issues of existing RNA pesticides by using surface display. On the other hand, we need to carefully consider production costs and their specifics.
Why did we establish contact?
Professor Takemoto specializes in RNA pesticides. We interviewed him to find out how well our concept would work, particularly in terms of its mechanism of action.
What we learned
- In RNA pesticides for rice blast disease, targeting melanin synthesis is straightforward. The color of melanin is easy to evaluate and can be quantitatively assessed. In comparison, MoDES1 is difficult to evaluate (it depends on how healthy the plant is) and is not the best target. It would be better to select targets by considering which part of the infection mechanism of rice blast disease to suppress.
- If you’re damaging the surface via surface display to allow the plant to take up RNA, there’s concern about damage to the plant. If you’re going to use surface display, it might be better to attach something that is easily taken up by the pathogen or something that breaks down the cell wall of the pathogen.
- It is also unknown how much RNA can be maintained within the membrane vesicle. In the field, you need to check whether other organisms affect the target gene. Additionally, since there might be strong microorganisms that degrade RNA, you need to be mindful of residual efficacy.
- As for the problems with current RNA pesticides, they cannot compete with the cost of chemical pesticides. Long-term storage is also difficult. Since they don’t persist well, their effects do not last long.
- Resistant strains also emerge with RNA pesticides. In insects, for example, they develop resistance by no longer taking up the RNA, so adding functions to enhance uptake is a good idea in that sense.
Reflection
We need to reconsider the target gene. Regarding surface display, we also need to explore methods to reduce damage to the plant. As for implementation aspects, there were discrepancies with opinions from previous interviews, so we need to examine this carefully.
Why did we establish contact?
We envision that the RNA pesticides developed through our technology will eventually reach farmers. Therefore, we had to evaluate the pesticides we aim to create from the farmers’ perspective. Additionally, it is crucial to evaluate pesticides in terms of resistant bacteria and environmental issues. To gain further insight, We decided to speak with JA ZEN-NOH, which is responsible for economic activities such as the sale of agricultural and livestock products and the supply of agricultural materials within the JA (Japan Agricultural Cooperatives) Group.
What we learned
- Due to the aging of farmers and lack of successors, they want to easereduce the physical burden of tasks such as pesticide application, so they are increasingly adopting IPM (Integrated Pest Management). Here, pesticides that are used less frequently and are much saferharmless are in demand.
- For ensuring the safety and quality of pesticides, and their safe and proper useRegarding environmental impact and regulations, Japan has “Agricultural Chemicals Regulation Act”. Currently, there is a worldwide trend toward an increase in the data required for safety, with a corresponding rise in development costs and a sharp increase in raw material costs, which has led to a the price increase of pesticides has become an issue.Globally, there is a trend toward increasing the amount of data required to ensure safety, leading to rising development costs and increasing pesticide prices.
- Chemical pesticides may lead to the emergence of resistant bacteria or resistant pests. Furthermore, there are few effective pesticides against viruses, bacteria, and soil diseasespathogens in the soil.
- RNA pesticides are a new technology that has not yet been commercialized in Japan, and It is necessary to take time to deepen our understanding of safety and the risks associated with useit will take time to deepen understanding.
Reflection
RNA pesticides may provide a new solution for pests and diseases that chemical pesticides have not been able to handle. However, since we are working on developing pesticides, we must carefully consider the burden on farmers who will apply them. Moreover, since farmers are directly involved in applying pesticides, we need to be particularly cautious about their safety. Further investigation into the safety and testing methods of RNA pesticides will be necessary as we move forward.
Why did we establish contact?
Understanding the state of the pesticide industry is crucial when developing pesticides. We sought advice on the impact and feasibility of our pesticide concept from someone leading a pesticide project who is always striving to meet customer needs. (The recipient has requested to remain anonymous.)
What we learned
- Japan is a rice-producing country, and since rice is the staple food, it is cheaper compared to other crops. Therefore, pesticides for rice must also be affordable to be accepted. Current rice pesticides can be applied simultaneously with rice planting, but RNA pesticides offer fewer advantages compared to conventional methods.
- The cost of pesticides needs to be kept around 3 to 5 percent of the total cost. Alternatively, the value must be commensurate with the price. In any case, it is necessary to compare the cost per hectare with competitors, but it is doubtful that RNA pesticides for rice blast disease can compete at that level.
- Consideration must also be given to the storage of RNA pesticides. Rice pesticides can be stored for at least four years. Biological control agents only last for about a week, requiring a cold chain specifically for them, and no stock is held. A similar supply chain would likely be needed for RNA pesticides.
- If the implementation cost of RNA pesticides is high, targeting high-value crops might allow for the promotion of RNA pesticides’ safety benefits, which could be advantageous.
- Some farmers may be interested in RNA pesticides, but certain consumers are sensitive to such innovations.
Reflection
The interview suggested that RNA pesticides differ in many aspects from chemical pesticides, such as the target market and delivery methods. It is anticipated that it will be difficult for RNA pesticides to compete at the same price level as chemical pesticides for rice blast disease. We will need to broaden our scope beyond rice blast disease to other plant diseases.
Why did we establish contact?
Kumiai Chemical Industry Co., Ltd. is a company engaged in pesticide development for the world in Japan. They handle everything from research and development of chemical compounds used in pesticides to the sales of pesticide products. Given their excellent technology in the development of new pesticides, we requested an interview to discuss RNA pesticides within the range they could share.
What we learned
- Even with conventional chemical pesticides, the effects must last for at least one month. If the proposed method can achieve this, it would have a significant impact. However, measures must be taken in formulation to prevent issues like being washed away by rain.
- Pesticides must meet safety standards set by the government.All chemicals have risks and no chemical is 100% safe. RNA pesticides are also chemical substances, so the risk is similar.
- It would be good if RNA pesticides could control what chemical pesticides cannot control. However, it is good to be able to change the site of action just by slightly changing the RNA sequence. If they are effective against pests, diseases and weeds that chemical pesticides cannot fully control, that would be even better.
- It would be better to consider RNA pesticides for pathogens that chemical pesticides are ineffective against (It is unlikely that each company would simultaneously market pesticides for rice blast disease as both chemical pesticides and RNA pesticides.). Targeting pests that rapidly develop resistance would be a good strategy (refer to FRAC).
- Cost is an issue when it comes to pesticides. In the case of pharmaceuticals, even if they are expensive, they are still sold due to their necessity, but this is not always the case with pesticides. The lower the cost of pesticides, the better. If there is a breakthrough that allows RNA pesticides to be produced more affordably and stably, they could spread rapidly.
Reflection
We were able to confirm the minimum required functions for a pesticide, such as the duration of effectiveness. On the other hand, it was again suggested that rice blast disease may not be the optimal target for RNA pesticides. Furthermore, the safety of RNA pesticides will likely need to be addressed through testing. The discovery that chemical pesticides and RNA pesticides could coexist was another important insight for us.
Check
While our project concept of encapsulating RNA in surface-displayed MV was suggested to be appropriate, we realized the need to reconsider production costs, efficiency, and targets when considering implementation on farms. In particular, it was pointed out that rice blast disease might not be an appropriate subject as a first choice when considering the situation in Japan. On the other hand, we learned that there are many plant diseases for which RNA pesticides are needed, such as viruses, bacteria, and soil-borne pathogens, and we felt the necessity for RNA pesticides.
Act
We need to reconsider what our project should target, including the necessity of focusing solely on a specific disease like rice blast. Therefore, we decided to return to the opportunity identification stage.
Sec4: Identify opportunities
Plan
RNA pesticides for rice blast disease may not be effective in terms of needs, so we reconsidered what kind of project we should handle. We decided to focus on examining what role RNA pesticides or pesticides in general should play in society.
Do
Why did we establish contact?
The Ministry of Agriculture, Forestry and Fisheries (MAFF), Japan’s agricultural authority, has demonstrated significant interest in the implementation of RNA pesticides under its “MIDORI Strategy for Sustainable Food Systems”. By speaking with the relevant government officials, we aimed to clarify the needs for RNA pesticides and the requirements that must be met for their implementation.
What we learned
- In the United States, three companies are already developing RNA pesticides, and a pesticide for potato targeting Colorado potato beetle has been approved by the EPA. In Japan, no RNA pesticides have yet been registered, and they are still in the research stage. Since RNA breaks down easily in nature, the challenge lies in determining how to make it effective.
- Since rice blast disease is an important disease in Japan, control measures have been established for a long time, and no major damage has occurred in recent years because sufficient preventative measures have been taken by individual farmers. However, in light of recent climate change there is a risk that rice blast outbreaks may increase, and there may be situations where conventional pest control measures will not be sufficient in the future. It is necessary to update pests and diseases control measures, and RNA pesticides could play a significant role in this regard.
- The Ministry of Agriculture, Forestry and Fisheries (MAFF) designates 157 harmful pests and diseases as “plants and animals designated as harmful species” for which special countermeasures are required for the pest control since the distribution in Japan is not isolated or not likely to be isolated, and tend to spread quickly and cause serious damage to crops under Plant Protection Act.[4]
- For farmers, user-friendly pesticides are cheap, effective against various pests and diseases, and require only one application. In the future, Implementation of RNA pesticides should be considered, such as mixing various types of RNA pesticides to deal with a variety of diseases.
- The examination for the registration of pesticides is divided among the relevant ministries. MAFF handles pesticide applications, assesses the impact on workers and bees, and registers pesticides. The Ministry of the Environment examines the impact on aquatic life, birds, and river water. The Consumer Affairs Agency and the Food Safety Commission evaluate whether the pesticide is safe for consumption and whether any residues pose a risk.
- The MIDORI Strategy for Sustainable Food Systems targets 50% reduction in risk-weighted use of chemical pesticides by 2050. In this context, “risk-weighted use” is based on ADI (Acceptable Daily Intake), which is the amount of a substance that can be consumed daily over a lifetime without adverse health effects. In Japan, there is no experience in hazard characterization for RNA pesticides, so it is difficult to predict what value of ADI will be set.
- Pesticide development takes 10 years and costs in the billions to tens of billions of yen. Resistance is a challenge for chemical pesticides, so manufactures need to develop sale strategies taking into account the development of pesticide resistance that match development costs. As regulatory requirements increase, so do development costs, making it difficult for all but the largest companies to develop new pesticides.
- The tightening of pesticide regulations is influenced by cultural factors. Some countries impose strict pesticide management policies for environmental conservation. However, in Japan’s climate(high temperature and humidity), which is prone to outbreaks of plant pests and diseases, applying similar regulations could hinder pests and diseases control in a timely and appropriate manner, thereby threatening the stable food supply that pesticides are intended to protect.
Reflection
We confirmed the need to consider pesticide options that balance pest control efficacy with environmental impact. We also gained insights into the current state of pesticide registration and the rising development costs due to stricter regulations. Additionally, it is important to focus on developing affordable, long-lasting pesticides that are effective against a wide range of pests and diseases to meet farmers’ needs.
Why did we establish contact?
We needed to gain a deeper understanding of the current state of pesticides and what is required for pesticide development.We had the opportunity to ask a company about that matter. (The recipient has requested to remain anonymous.)
What we learned
- Cost of pesticides per hectare needs to be kept below a certain price to remain competitive with other growers.
- The issue of resistance against pesticides has always existed. Some bacteria develop resistance more easily
than others. Currently, growers manage to reduce risks of resistance development by rotating use
active ingredients in pesticides. - Pesticides invariably affect the environment and the human body, for better or worse. Therefore, their use must be restricted by regulations. The Ministry of the Environment conducts Environmental Impact Assessment, and there is currently a movement to re-evaluate pesticide safety.
- One of the main drawbacks of RNA pesticides is their short duration of effect and short shelf life. Although RNA pesticide development is limited in Japan, it could become feasible with technological innovations. The current obstacles to advancing RNA pesticides include a lack of sufficient knowledge and the selective specificity of these pesticides.
- Chemical pesticides against bacteria certainly exist, but there is not an abundance of that types of pesticide. (in some cases, antibiotics used in medicine are applied). While resistant bacteria have emerged, the pesticides have not become completely ineffective.
- Pesticide development costs tens of billions of yen. From selecting a candidate to implementation, it typically takes about 10 years. This period includes field tests, toxicity tests, environmental tests, long-term toxicity tests, data collection for applications, and national reviews.
Reflection
We learned that RNA pesticides have not yet reached the implementation stage in Japan. As confirmed in our earlier interview with the Ministry of Agriculture, Forestry, and Fisheries, RNA pesticides hold great promise and are highly anticipated.
Why did we establish contact?
Syngenta Japan K.K. is a company engaged in the research, production, and sales of pesticides. They also agreed to participate in our interview. We continued to ask for their insights on the current state of pesticides and their technical characteristics.
What we learned
- It has become increasingly difficult to balance the safety and efficacy of pesticides compared to the past, and the research and development costs for creating a single compound are continually rising (due to the need to ensure safety). In the medium to long term, it would not be surprising if issues arise that current solutions cannot address. These issues could stem from complex factors such as climate change. (This highlights the need to develop pesticides that can respond to sudden changes.)
- It would be beneficial to have a testing system that considers the life cycle of pathogens. The first priority is validation of technical feasibility. There is a significant need to examine whether a model testing system can be established under dry conditions. Further study is needed on how changes in pH will affect the system, as well as whether the pesticides are stable in liquid formulation and can withstand dry conditions.
- Regarding the characteristics of pesticides, spraying is more common than absorption by plants. Recently, drone application has also become more frequent. Storage stability is a challenge when get into developmental stage of RNAi(how long the pesticides can be stored in a warehouse as inventory).
Reflection
We realized that it has become more difficult to balance the safety and efficacy of pesticides. Additionally, from a more technical perspective, we recognized the need to develop specific testing systems to create a robust framework.
Based on the interviews from Section 3 onward, which led us to revisit our concept, we first organized the needs and issues surrounding pesticides and RNA pesticides. We then decided to discuss again the points that we might be able to address.
Needs and Issues in Pesticides and RNA Pesticides:
| Theme | Points |
|---|---|
| Needs for Pesticides | • Pesticides are indispensable for a stable food supply. • For farmers, keeping the cost of pesticides low is crucial; specifically, it needs to be maintained at about 3–5% of the total agricultural costs. • Pesticides that have long-lasting effects with a single application are desired. Additionally, effectiveness against various pests and diseases is expected. • Safe pesticides with minimal impact on humans and the environment are desired. |
| Trends and Issues in Pesticides | • Regulations regarding environmental impact and food safety are being tightened, leading to an increase in safety data requirements. • Resistant strains against chemical pesticides are emerging, necessitating the development of new control methods. • The development of pesticides now takes about 10 years and costs several billion yen, making it feasible only for major manufacturers. • Control of pests and diseases that cannot be addressed with conventional pesticides—such as viruses, bacteria, and soil pathogens—is a challenge. • In the United States, RNA pesticides have already been approved by the EPA, and attention is increasing for RNA pesticides in Japan as well. |
| Needs for RNA Pesticides | • In response to the issue of resistant strains against existing chemical pesticides, RNA pesticides can address this by simply changing the sequence of the target gene, making them promising for managing resistant strains. • Compared to chemical pesticides, RNA pesticides are easily degradable and have less environmental impact, leading to high expectations for safety for humans and the environment. |
| Trends and Issues in RNA Pesticides | • RNA is easily degradable, and the short duration of its effectiveness is a challenge. • Although the production cost of RNA pesticides is decreasing, the implementation cost is currently high, posing an economic burden for farmers. • Research on RNA pesticides is currently biased towards insects. Effective delivery is a challenge because penetrating fungal cell walls is difficult. • Selecting appropriate target genes is challenging, requiring research to maximize effectiveness against specific pests and diseases. • Long-term storage of RNA pesticides is difficult, potentially necessitating a specialized supply chain. • As a new technology, it may take time for acceptance by farmers and consumers. |
Based on these points, we discussed areas where we might have opportunities to provide solutions and reached the following conclusions:
- RNA pesticides are an effective option for addressing pests and diseases that cannot be managed by chemical pesticides, including safety concerns and resistant strains, which are issues with existing pesticides.
- However, RNA pesticides currently do not meet the required persistence and cost-effectiveness needed for pesticides , so these issues need to be resolved. Particularly, enhancing persistence is extremely important; by improving it, the total amount required for application decreases, and even if RNA pesticides are somewhat more expensive, they could become an option for farmers due to the balance of benefits.
- Solving the persistence issue of RNA pesticides is the first and most crucial step . Upon resolving this, we can then reach the stage of discussing other issues related to RNA pesticides. Next, we should consider reducing costs, as it is an extremely important factor in the implementation of pesticides.
- Research on RNA pesticides is biased toward those targeting insects . However, considering the needs for pesticides, RNA pesticides that are effective against fungi and soil-borne diseases should also be explored.
Check
Through interviews with the Ministry of Agriculture, Forestry and Fisheries and pesticide companies, we were able to understand RNA pesticides in the context of conventional pesticides. Additionally, based on the interviews from Sec3 onwards, we confirmed that increasing the durability of RNA pesticides and reducing costs is an appropriate direction for considering the role that RNA pesticides should play and for our project to support that. We also thought it necessary to pay attention to the direction of effectiveness against fungi.
Act
Our project has decided to address the challenges of durability and cost, which are particularly problematic for RNA pesticides, as a technology to “implement RNA pesticides”. Moving forward, we will verify whether this concept of “implementing RNA pesticides” is feasible.
Sec5: Create concepts
Plan
We will consider what kind of concept would be preferable to imagine regarding the issues of RNA pesticide durability, cost, and other points that became clear in Sec4.
Do
Our initially considered concept, apart from the aspect of rice blast disease, focused on improving the persistence of RNA pesticides. Moreover, the proteins that can be displayed via surface presentation—designed to infiltrate the rice blast fungus—are not limited to a single type; by changing the plasmid sequence, they can be replaced with others. Additionally, in terms of productivity, the method we use (PIA-MVP) can produce RNA relatively efficiently. We have designed the following concept as an improved version of our previous one.
Our concept is designed to solve issues associated with pesticides; however, it lacks specifics on how to target which diseases and how to access them. To address this problem, we decided to create platform software that can propose candidates for the contents of the modules. Additionally, we decided to introduce an economic model to examine economic feasibility.
Check
Based on our knowledge so far, we have developed a concept called MOVE. This includes the idea of encapsulating shRNA in surface-displayed MV, as well as an RNA pesticide platform and an economic model for production.
Act
We will verify whether this concept can meet the needs for pesticides and solve the problems that existing pesticides face.
Sec6: Validate concepts
Plan
We will verify whether the concept we have created actually works.
Do
Why did we establish contact?
Hokusan Co., Ltd. is a company based in Hokkaido, Japan. They are engaged in research, production, and sales of pesticides, as well as animal medications, and operate closely with the local community. Hokkaido, located in northern Japan, has a colder climate compared to Honshu. Therefore, the crops grown and the diseases that arise may differ. Since we need to learn more about diseases that are difficult to manage with chemical pesticides, we sought their advice on this topic. (The recipient has requested to remain anonymous on their names.)
What we learned
- For soil bacteria, pesticides need to be applied directly into the soil, but because the pesticide is absorbed by the soil, it is difficult to achieve satisfactory effects at the field level.
- Sugar beets are currently suffering from diseases. Resistant fungi (filamentous fungi) have emerged against various pesticides, but RNA pesticides could be valuable in addressing these types of diseases.
- In potatoes, scab disease significantly reduces the market value. Some well-known potato varieties are particularly susceptible to scab. In Japan, popular branded varieties of potatoes and other crops tend to sell well, so RNA pesticides could become a strong solution for this issue.
- When developing pesticides, it is essential to consider the factors of AI (active ingredients) and DDS (drug delivery systems) separately, with feasibility and complexity in mind. It is necessary to evaluate whether the technology is in the stage of science or technology and assess its feasibility. Consideration should also be given to the time and cost involved.
- In the case of MOVE, both the active ingredient RNA and the delivery system (surface-presenting MV) are still more in the science phase. However, there is potential for extending the duration of effectiveness, and costs may decrease. Efforts should be focused on research to increase feasibility.
Reflection
We are confident that our concept could be an effective solution for crops like sugar beets and potatoes when considering the actual market. On the other hand, as the technology is still in development, diligent research and development are necessary.
Why did we establish contact?
Mitsui Chemicals Crop & Life Solutions is a major company in Japan’s agrochemical industry. Our goal was to gather information about the current challenges and concerns regarding MOVE and RNA pesticides, particularly regarding safety concerns, regulatory status, and market acceptance.
What we learned
- Concerns regarding RNA pesticides include the target organism’s resistance, residual effectiveness, and whether they can be manufactured in large quantities at low cost, that is, whether the pesticide can be provided at a price acceptable to the market. Furthermore, it is unclear whether RNA pesticides will be accepted by the public in Japan.
- RNA pesticides may have a positive impact on diseases that have been difficult to control up until now, due to the high selectivity of RNA pesticides
- While chemical pesticides involve synthesizing chemical substances, screening them for efficacy against pests, optimizing their structures, and confirming their effects, RNA pesticides target the genes of specific enzymes or receptors. The development period for RNA sequences may be shorter.
- Since pesticide registration systems differ by country, some countries have relaxed evaluation standards for biopesticides. However, it remains unclear how RNA pesticides will be evaluated in various countries. It is expected that RNA pesticides will be held to the same safety standards as chemical pesticides.
- In Japan and other countries, pesticide registration standards are becoming stricter, and there is also a re-evaluation system (where approval must be obtained again after a certain period). Europe, in particular, is placing a strong emphasis on environmental conservation. It is also necessary to gain the understanding of environmental groups.
Reflection
We reaffirmed that MOVE must overcome challenges not only in terms of cost-effective production and efficacy but also in ensuring safety. Although RNA pesticides are theoretically safe, they cannot be trusted without proper testing. We must assess the safety of RNA pesticides with an extremely neutral perspective rather than blindly trusting their safety.
Why did we establish contact?
Professor Yasui is a researcher studying the medical applications of membrane vesicle. We interviewed him about the technical aspects of our concept.
What we learned
-
It is more effective to screen bacterial strains that produce MV and are easily taken up by fungi (for example, experimenting with both Gram-negative and Gram-positive bacteria to phylogenetically explore those that are readily internalized). The uptake efficiency of MV by fungi is usually around 2–3%, and about 10% in the best cases. Using liposomes is also an option (they likely have higher uptake efficiency).
-
Regarding MV purification and confirmation of the RNA content, the basic method is to collect MV via ultracentrifugation and verify the internal RNA using qPCR. To be certain about the presence or absence of RNA, a large number of samples must be tested.
-
Concerning the functionality of RNA-encapsulating MV, they last about one week at 4°C in their natural state (uncertain at room temperature). Adding an extra 2–3 nucleotides to the RNA ends significantly increases the retention period. Long-term storage is also possible by freeze-drying. The uptake of MV by fungi occurs in about six hours.
Reflection
The feasibility of MOVE becomes tangible through experimentation. The information on specific methods for MV purification and RNA verification (ultracentrifugation and qPCR) is highly valuable for experimental design. Additionally, insights into screening for strains that are easily internalized and the stability of RNA-encapsulating MV—particularly storage methods and strategies to extend retention periods (such as adding nucleotides to the RNA ends)—have provided important guidance for implementing our concept.
Check
We found that our concept is not deviating from the major direction that pesticides should aim for. While there are technical challenges related to the production and delivery of RNA pesticides using MV, we confirmed that these are within a solvable range. We need to verify through experiments whether the concept will work well.
Act
From here, we will move on to the actual development of the solution. We will create a plan summarizing the situation so far, and then put our hands to work.
Sec7: Develop solutions
Plan
As the solution, we ultimately decided to carry out a project with an overall picture as described in the Description . Our project can be briefly summarized as consisting of the following three elements:
- Development of MOVE
- Cost estimation for pesticide implementation using an economic model
- Development of an RNA pesticide database
Do
We discussed our experiments, taking into account the interviews we’ve conducted so far. Our final experimental plans and results regarding the encapsulation of RNA into MV and the expression experiments of surface-displayed proteins are detailed in the Results section . Additionally, the actual progress of our experiments is presented in the Experiments section . For the economic model, please refer to Model , and for the database, see Software .
Check
Based on the interviews and discussions we’ve had so far, we made efforts to develop our solution by actually putting our hands to work according to the experimental design we created.
Act
We will understand what kind of impact this solution would have when it is actually implemented.
Sec8: Deploy solutions
Plan
How will MOVE impact society? We need to consider a world where MOVE has actually been realized in order to think about this. We will clarify the benefits of implementation and the challenges that need to be overcome for implementation. Since it is difficult to achieve social implementation in this iGEM cycle, for the introduction of our solution, we will theoretically consider the impact based on interviews and experimental results.
Do
Why did we establish contact?
BoZo Research Center is a CRO offering preclinical research services for drugs, regenerative medicines, medical devices, agrochemicals and foodstuffs. Their service portfolio includes safety and genotoxicity studies, and chemical and bioanalysis using various methods. They also offer in-vitro and in vivo models of rats and mice for performing preclinical studies for drugs against cancer, metabolic diseases, and vaccines. We visited them to learn about the actual testing process.
What we learned
- In terms of safety, the indicators include:
Non Observed Adverse Effect Level (NOAEL): The maximum dose at which no harmful effects are observed in test animals.
Safety Factor: A number used to estimate human impact from the NOAEL in animals. Generally, this number is 100.
Acceptable Daily Intake (ADI): The amount of a substance a person can ingest daily without harm, calculated by dividing the NOAEL by the safety factor.
Maximum Residue Limit (MRL): The maximum concentration of pesticide residues, adjusted to ensure that human intake does not exceed the ADI. - Various types of toxicity tests are conducted, and the ADI is determined from the lowest NOAEL. However, if both genotoxicity and carcinogenicity tests return positive, development must be stopped. If either the genotoxicity or carcinogenicity tests are negative, ADI can be set, allowing development to continue (but development is often halted if genotoxicity tests are positive).
- It is anticipated that RNA pesticides may be evaluated similarly to nucleic acid-based drugs. Although MOVE (the subject of evaluation) must undergo standard pesticide testing procedures, changes to the RNA content may only require a literature review. The off-target effects due to hybridization will need to be assessed.
Reflection
MOVE must first undergo extensive environmental impact testing. Only after confirming that there are no toxic effects can it be used. When altering the external surface display proteins, a similarly extensive test may be required, but if only the internal RNA is modified, a simpler testing is expected to suffice. Testing and implementation should be carried out in accordance with the actual legal framework.
Why did we establish contact?
NIHON NOHYAKU is one of Japan’s leading pesticide manufacturers. We wanted to confirm how this project would be perceived from the perspective of a pesticide manufacturer.
What we learned
- Due to the characteristics of RNA pesticides, there is a higher possibility that the registration process could be shortened compared to other pesticides. If the RNA is carefully selected to target specific genes, it may be effective even with a small number of molecules.
- Genetic modification is already an established technology in industries such as detergents, pharmaceuticals, and industrial products. Similarly, effective communication is important to ensure that RNA pesticides are properly understood by stakeholders.
Reflection
MOVE may have the potential to avoid regulatory restrictions and demonstrate sufficient efficacy. This suggests a simple yet highly effective implementation. Additionally, effective communication with various stakeholders, including consumers, is crucial for smoother societal adaptation.
Why did we establish contact?
JA Chiba is the Japan Agricultural Cooperatives in Chiba Prefecture, located adjacent to Tokyo, the capital of Japan. We conducted an interview to identify specific diseases that should be targeted when MOVE is implemented.
What we learned
- The following diseases or pathogens are difficult to control:
| Crops | Diseases |
|---|---|
| White radish | Root diseases : Rhizoctonia solani, Bacterial soft rot Leaf diseases : Bacterial leaf spot |
| Cabbage | Root diseases : Clubroot(Bacteria) Leaf diseases : Sclerotinia rot(mold),Black rot(Bacteria) |
| Leek | Root diseases : Southern blight(mold),Botrytis squamosa,Bacterial soft rot Leaf diseases : Rust(mold), Alternaria leaf spot(mold), Downy mildew |
| Carrot | Root diseases : Black blotted root rot(mold) Leaf diseases : Leaf blight(mold) |
| Sweet potato | Root diseases : Foot rot(mold), Stem rot(mold) |
| Tomato | Root diseases : Bacterial wilt, Viral diseases Leaf diseases : Leaf mold, Cercospora leaf mold, Gray mold |
| Pear | Root diseases : root rot(mold) Leaf and stem diseases : Scab(mold) |
| Cucumber | Leaf diseases : Powdery mildew, Downy mildew, Gray mold, Sclerotinia rot(mold),Viral diseases |
| Rice | Blast disease(mold), Stem rot(mold) |
- Farmers are motivated by products that are highly effective and provide long-lasting control.
Reflection
This interview allowed us to learn about many difficult-to-control diseases. It is expected that by applying MOVE to various diseases, as listed above, RNA pesticides will have a significant impact. MOVE’s strength lies in its readiness to target a wide range of diseases.
Check
We were able to examine MOVE from various perspectives including inspection, business, and users. The advantages of implementation include the possibility of bypassing regulations and the predictable applicability to many types of plant diseases and pests. On the other hand, there are many uncertainties regarding inspection, and since there isn’t a single target, it’s possible that each module may not be optimized. We need to reduce challenges and enhance strengths through future technological advancements.
Act
We will create an implementation plan and a business plan. In Implementation, we introduce the implementation plan for MOVE. In Entrepreneurship, we introduce the business plan.
Check
Potentialities & Limitations
Our project ultimately took the form described in the Description section. The social value of MOVE, as gained through our Human Practices, is as follows:
- New Solution for Previously Untreatable Diseases : Can potentially provide effective countermeasures against viruses, bacteria, and soil-borne diseases that are difficult to treat with current chemical pesticides.
- Addressing the Issue of Resistant Pathogens : By simply changing the sequence of the target gene, it’s possible to respond to resistant pathogens, allowing for sustainable pest control.
- Reduced Environmental Impact : RNA pesticides are more easily degradable compared to chemical pesticides, resulting in less environmental impact and contributing to sustainable agriculture.
- Accelerated Target Selection : RNA pesticides target specific genes, enabling rapid and cost-effective development of effective pesticides.
- Regulatory Bypass and Swift Implementation : Compared to conventional pesticides, there’s a possibility of easier regulatory clearance, provided appropriate testing and safety confirmation are conducted.
- Wide Applicability : Can be applied to many crops as it can be customized as modules for various plant diseases.
On the other hand, MOVE also has limitations. They are as follows:
- Technological Uncertainties : At the current technological level, the technique to stably encapsulate RNA in MV and deliver it to the target has not been established.
- Uncertainty in Production Costs : The technology for mass production and affordable supply is undetermined, potentially causing an economic burden for farmers.
- Safety Verification : RNA pesticides need to meet the same safety standards as chemical pesticides, requiring long-term testing and evaluation.
- Consumer Acceptance : Due to the novelty of RNA pesticides, understanding and acceptance by consumers and farmers are necessary, requiring educational activities to dispel misconceptions and alleviate concerns.
- Potential Ecosystem Impact : There are many unknowns about the behavior of RNA pesticides in the environment and their effects on other organisms, with the possibility of unexpected side effects.
Self-Assessment
We evaluated our Human Practices operational framework according to the Human Practices Maturity Model published by iGEM[5] . For discussions on why we chose this evaluation metric, please refer to Innovation Management .
Human Practices Maturity Model
Maturity of HP Work 1 - Reflecting on design decisions
| Level | Description |
|---|---|
| Low Level | No actions to consider social-environmental context of the project to inform project decisions. |
| Low-mid level | Some limited engagement with stakeholders to inform basic design decisions. |
| Mid-level | Early stakeholder engagement to inform basic design decisions. |
| Mid-high level | Early stakeholder engagement; Comprehensive and holistic implementation in project design; Limited documentation. |
| High level | Extensive and transparent documentation; Iterative stakeholder engagement; comprehensive and holistic implementation in project design. |
Maturity of HP Work 2 - Exploring and reflecting on context beyond the lab
| Level | Description |
|---|---|
| Low Level | No actions to understand contexts. |
| Low-mid level | Partially understanding the contexts of the project but not so detailed, complete or not so related; the information is mainly collected by secondary research. |
| Mid-level | Good understanding of the project’s context; Collect information by thorough research including primary research. |
| Mid-high level | Good understanding of the project’s context; Collect information by thorough research including primary research; Have good understanding about the relations between the contexts and projects. |
| High level | The requirement of Mid-high Level ; The knowledge of contexts help with the project design; (optional) Team even have reflective ideas about the contexts such as improving regulation. |
Maturity of HP Work 3 - Incorporating diverse perspectives
| Level | Description |
|---|---|
| Low Level | No effort to mapping stakeholders (industry / markets, communities, individuals, etc) that would be affected by the project. |
| Low-mid level | Demonstrate robust rationale for identifying stakeholders; mapping stakeholders (industry / markets, communities, individuals, etc) that would be affected by the project, their relationship with themselves and with the team; list some of their understandings and real needs based on efforts to engage with them. |
| Mid-level | Demonstrate robust rationale for reaching out stakeholders; - broaden perspectives by adding to the mapping communities and people who might not be affected, to know more about their perception of projects and other comment; list which perspective and options have been incorporated or not into the project. |
| Mid-high level | Engage with stakeholders in a participative and cooperative way, discussing their perspectives and needs; well document this process; exhibited the rationale behind the choices to incorporate or not the different perspectives; be critical in relation to the needs and perspectives of the diverse stakeholders and with what can actually be solved or not with the projects. |
| High level | Enlarge the ability to learn from and consult diverse communities and stakeholders, including those who might hold critical views towards the project; be able to develop feedback mechanisms that encourage stakeholders to participate in each project change; robust documentation on how the feedback was incorporated into the project. |
Maturity of HP Work 4 - Anticipating positive and negative impacts
| Level | Description |
|---|---|
| Low Level | Not present any reflection on possible positive or negative impacts of the project. |
| Low-mid level | At some point in development, lists some positive and negative impacts that the project can have in general terms. |
| Mid-level | Anticipate positive and negative impacts from the beginning of the project; consider different dimensions (economic, social, scientific, educational, etc.); constantly adapting the list of impacts according to the development of the project. |
| Mid-high level | Demonstrate the willingness, capabilities and skills to either alter the project or develop sufficient countermeasures to mitigate such risk when the technique/knowledge developed by the project is likely, no matter how remotely, to be misused or create ethical, social, legal problems. |
| High level | Engaging with relevant stakeholders to find alternatives that would reduce risk whist increasing benefits, allowing project to progress. |
Maturity of HP Work 5 - Responding to human practices work
| Level | Description |
|---|---|
| Low Level | Do some human practices work; human Practices work have not been integrated in to projects, or have not been exhibited through documentation. |
| Low-mid level | Do good human practices work; these works are partially integrated into projects design/execution; documentation of this process. |
| Mid-level | Do good human practices work from the beginning; these works are mainly integrated into later stage (execution) of projects; good documentation of this process. |
| Mid-high level | Do good human practices work from the beginning; these works can and have been integrated into early stage of projects (purpose/design); good documentation with some reflection. |
| High level | Human practices work plays a substantial role in team’s scientific, technical, safety and/or communication decisions, from the project’s beginning to its end. |
Maturity of HP Work 6 - Approaching limitations with integrity
| Level | Description |
|---|---|
| Low Level | No consideration of project limitations. |
| Low-mid level | Notional consideration of project limitations; no alternatives proposed. |
| Mid-level | Basic analysis of project’s strengths and weaknesses. |
| Mid-high level | Advanced and transparent examination of strengths and weaknesses; assessment of improvement areas and potential; basic adjustments of project. |
| High level | Transparent assessment of strengths, weaknesses, opportunities and threats of the project; assessment of improvement areas and potential; documented roadmap of adapting project to opportunities and threats. |
Other Consideration: Creativity and Originality
Originality/unusual approaches without precedence within iGEM is a sign of maturity in advanced innovative thinking. This presents another feat of higher advanced maturity.
| Criteria | Level | Reason |
|---|---|---|
| Reflecting on design decisions | High | From the early stages of the project, we engaged comprehensively with stakeholders and collected valuable insights for designing pesticide durability and cost reduction. The design decisions reflect the opinions of on-site users and pesticide companies, and social and environmental contexts are also considered. Extensive and transparent documentation has also been carried out. |
| Exploring and reflecting on context beyond the lab | High | Deeply understanding the context of the project, we are gathering information from various aspects such as the pesticide market, legal regulations, environmental issues, and consumer perceptions. We have directly obtained information from a diverse range of stakeholders including the Ministry of Agriculture, Forestry and Fisheries, pesticide companies, and agricultural cooperatives, and have reflected this in the project design. Based on this knowledge, we have reached a level where we can propose improvements regarding current regulations and environmental impacts. |
| Incorporating diverse perspectives | High | Actively mapping the diverse stakeholders affected by the project, we are collecting opinions from farmers, pesticide companies, agricultural organizations, government officials, and others. We demonstrate an attitude of incorporating the views of a wide range of stakeholders, including those with critical perspectives, into the project. We critically examine and address the needs and issues of each stakeholder. |
| Anticipating positive and negative impacts | Mid-high | From the early stages of the project, we have been anticipating impacts in various aspects, including social and economic effects. We also show a willingness to consider countermeasures against environmental impacts and burdens on farmers. However, there is still room for further efforts in formulating specific countermeasures to mitigate actual risks. |
| Responding to human practices work | High | From the early stages of the project, we have been engaged in human practices work, integrating stakeholder feedback into the project’s objectives and design. The human practices efforts have played a significant role in scientific, technical, and communicative decision-making. |
| Approaching limitations with integrity | Mid-high | With transparency, we are evaluating the strengths and weaknesses of the project and considering possibilities for improvement. We are also making fundamental adjustments to challenges such as technical limitations and production costs. However, the documentation of a clear roadmap to adapt the project to opportunities and threats has not been fully completed yet. |
| Other Consideration: Creativity and Originality | High | The concept of MOVE is unique in that it utilizes MV to enhance the durability of RNA pesticides, bringing a new approach to the pesticide industry. Particularly, the ideas of designing as modules and platformization are innovative initiatives unprecedented in iGEM. |
Act
After considering the strengths we should enhance and the weaknesses we should overcome in our current Human Practices, we leave the following recommendations for future activities.
- By contacting diverse stakeholders such as users, related companies, and government agencies from the early stages of the project and reflecting their feedback in the design, we can build more practical and effective solutions.
- Actively incorporating critical opinions from diverse stakeholders and refining the project leads to a more trustworthy and feasible project.
- Not only predicting the risks and impacts of the project but also establishing specific risk mitigation measures early on can enhance the durability and safety of the project.
- By documenting a long-term roadmap that can flexibly respond to the external environment based on the project’s strengths and challenges, we can strengthen our growth strategy and adaptability.
- Unique ideas and platform initiatives like MOVE create unparalleled value and enhance competitiveness, so it’s important to continue seeking innovative ideas in the future.
- In the progression of the project, maintaining constant discussions both within and outside the team, and regularly evaluating and improving strengths and weaknesses greatly contributes to the project’s success.
Additionally, regarding the lack of risk mitigation measures and long-term roadmaps that were insufficient in our project, we are discussing and considering specific measures in the Implementation phase.
References
[1] International Organization for Standardization, https://www.iso.org/obp/ui/#iso:std:iso:56000:ed-1:v1:en:term:3.1.1
[2] Japan Innovation Network, “わかりやすいイノベーション・マネジメントシステム”, 2024
[3] 2023 Mcgill, Integrated Human Practices, https://2023.igem.wiki/mcgill/human-practices/
[4] Ministry of Agriculture, Forestry and Fisheries, “指定有害動植物について”,
https://www.maff.go.jp/j/syouan/syokubo/gaicyu/g_yosatsu/
[5] iGEM, “Human Practices Matuality Model”, https://responsibility.igem.org/human-practices/maturity-model