Our team was fortunate to have several opportunities to meet with professionals. We had the chance to: 1) discuss our vision and project goals; 2) learn from their expertise and use that knowledge to further develop our project; 3) share ideas; and 4) make contacts for potential future collaborations. These encounterswere valuable (or precious) to us and helped make our project better. All these meetings have allowed us to think about integrating the investigated issues into the design and execution of our project. We want to thank all the professionals with whom we exchanged and especially thank the Rathenau Institute for all their help. During the summer, we worked with Mrs. Zoe ROBAEY from the Ratheneau institut, who was a great help for the development of our application scenarios and the techno moral scenario. If you want know more about this collaboration click the fixed menu on the left.
Vector-borne diseases are a major global health burden. One of the most dangerous vectors is the mosquito, which is responsible for more than one million deaths annually. After taking a blood meal on an infected individual, the mosquito carrying the pathogenic agent can transmit the pathogen to another host during a new bite. Despite intense research, vaccines and/or treatments are still needed, thus, the fight against these deadly diseases relies mostly on vector control. One of the primary sources for wide spread vector control are the usage of insecticides. However, the over spraying of insecticides impacts the environment and leads to the selection of insecticide resistance mosquitoes. Therefore, we developed a novel diagnostic device, Mos(kit)o. This kit includes a fixed or mobile mosquito trap and a biosilica cellulose composite patch, produced by silica, which was the result of using genetically, modified E. coli. It was our intent to create a device that not only classified the vector-borne viruses circulating within specific regions but also provided a tool for local agencies to identify hot spots. This would allow for better targeting of insecticide spraying and it could help address public and environmental health concerns.
With the assistance of synthetic biology, we successfully modified E. coli, within a contained fully functioning biosafety laboratory. With it, we produce the protein needed to create biosilica, and bind antibodies onto a cellulose support. We selected biosilica to increase rigidity of our patch and because it is completely biodegradable. The innovative design of the patch creates a multilayered matrix coated with antibodies capable of detecting a wide panel of vector-borne pathogens and insecticide resistant proteins from captured mosquitoes. This patch is customizable and can be easily adapted to simultaneously test for multiple vector-borne pathogens prevalent in specific locations. Additionally, the patch will have 2D barcoded readouts, generating an environmental surveillance database. A precise map of vector hot spots will provide a better assessment and response to vector-borne diseases, assisting local health authorities with anticipating and preparing for an epidemic. The development of our project’s concept and the design of our device (i.e. patch and trap) was an iteractive process that involved a multidimensional collaboration of people and ideas. We successfully achieved this through: 1) numerous team brainstorming activities; 2) oral and poster presentations to various audiences (i.e. scientists, young researchers, professionals, and students); 3) organizing meetings with scientific experts (i.e. ecologists, entomologists); 4) consulting local agencies (French Interdepartmental Mosquito Control Board (EID) and in the United States the New Orleans Mosquito Control Board) and a drone company to discuss our project and if applicable, potential collaboration. For more information go to the METHODOLOGY setion. Additionally, we incorporated surveys assessing the general public’s understanding and acceptance of synthetic biology. These steps were essential to ensuring we gathered knowledge, gained feedback, and considered as many options as possible; making necessary adjustments based on our findings. Our tool will be user-friendly, safe, and applicable.
The Mos(kit)o device is easy to use and it does not require scientific expertise so it is possible to train people locally. From the set up of the trap to the analysis of the patch, the steps are simple and designed to reduce user error. For example, the quick read function has a color change component to ensure quick and accurate interpretation of results; changing from no color to color for positive results. For more information go to the DEVICES setion.
In the Laboratory The students working on this project received laboratory safety training and were supervised during all experiments. All manipulations involving GMOs only took place in a contained biosafety level II laboratory and the usage of GMOs was only required for the production of the biosilica protein (made using E. coli bacteria). The protein was made in the cell and when the cell was lysed, the protein was released and the GMO destroyed. Therefore, there was no release of the GMO during this process. In the Field. All personnel using the Mos(kit)o will be trained to ensure proper usage of the device. The kits are designed to be safe and user friendly, requiring no scientific background. The operators will not have any contact with the infectious materials, reagents, or the newly produced protein.
Upon successful completion of our lab work and following informed discussions with stakeholders, we illustrated two application scenarios where the Mos(kit)o would be utilized: in developed countries and in developing countries. The diagram below explains the life cycle of our device, beginning with the production of the biosilica protein and concluding with real life applications and potential outcomes. Context 1 describes developed countries where agencies or municipalities like the Centers for Disease Control and Prevention (CDC) in the US or the French Interdepartmental Mosquito Control Board (EID), respond to emergencies. A warning is received from a specific location and these agencies are responsible for distributing the Mos(kit)o and ensuring that appropriate personnel are deployed to endemic areas. Currently, the CDC has an Epidemic Intelligence Service (EIS) that responds during public health outbreaks. They are responsible for identifying the causal agent(s) and they are tasked with assisting endemic areas with efforts to prevent and/or control the transmission of the disease(s). 2 A similar institutional set-up can be found in France. Following our conversation with a division director for mosquito preparedness at EID (acronym), we developed a practical example illustrating the utility of the Mos(kit)o device. Presently, administrators manually test endemic areas, which is labor and time intensive. The design of our device eliminates these conditions by using stationary traps and a patch capable of simultaneously detecting multiple viruses. Additionally, the division director of EID expressed interested in our device and suggested the need to have these traps within certain distances from hospitals where infected people are treated or airports because it is a transit place for global entry/exit from endemic areas. Our device would be used as an important proactive measure that could protect non-infected people if they are in close proximity to these particular hot spots (e.g. hospitals, airports) where infected mosquitoes are circulating. In scenario 1, these organizations have the resources to respond to the hazards, administer the kits, and analyze the results; making them ideal for Mos(kit)o. In Context 2 , which describes developing countries where access is not as easy and there are no local agencies as mentioned in scenario 1, the Ministry of Health, or equivalent instance, would assume responsibility for administering the kits. Personnel at the local Ministry of Health will be trained to properly set up the trap and on how to use the diagnostic device. We are aware that resources are limited in these settings; therefore, we designed the device to require minimum personnel for operation and to be low cost, user friendly, and safe. We were unable to discuss this specific scenario with a health ministry official to get their feedback, however, based on a conversation with tropical entomologists and the New Orleans Mosquito Control Board, which is solicited by the Brazilian government, we envisioned a situation in which a country receives a report of an outbreak of a vector-borne disease, like zika virus. In that case, the Ministry of Health would respond by requesting a Mos(kit)o device, either from the Mos(kit)o company or possibly a local NGO or CDC, with a stationary trap (for easily accessible areas) or a drone (capable of reaching remote areas). Upon arrival of the kit, trained local authorities will implement the trap in targeted locations and perform the required tests. An additional authorized person reads the results and the data will be entered into mapping software, capable of producing real-time updates. In both scenarios, the trained personnel will only have to inject specific syringes containing the reagents needed to test for various viruses, having no direct interaction with the mosquitoes, which are contained within the trapping device. Following use, the device will be returned to the distributing municipality/agency where it will be washed and reloaded. All waste will be properly treated and disposed of to eliminate the release of any pathogens in the environment. The data will be uploaded into a computer database for further analysis.
The data generated from the Mos(kit)o diagnostic device could be used as a global tool assisting with the environmental surveillance of vector-borne diseases. For example, the World Health Organization (WHO) is equipped with the resources to best manage, store, and protect the data. The WHO is responsible for supporting, responding, and communicating important information related to health to globally protect people. Our novel diagnostic device will: 1) assist with identifying regional hot spots allowing local authorities to quickly respond; 2) provide pertinent information pertaining to specific areas to target during insecticide spraying; 3) prevent the propagation of infected mosquitoes.
Disclaimer: The characters and US presidential setting is just a figment of our imagination. When: 2016 (Election year!!) Where: The USA Who: Mr. Bill Smith, Virginia Senator (Independent) and Presidential Candidate (Independent) Slogan: HELP ME. HELP YOU…TOWARDS A HEALTHIER TOMORROW FOR ALL. Personal statement from the candidate: “Scientists and researchers work tirelessly, trying to find cures for diseases that are killing and/or debilitating people. For some of you, this is personal because you, or your family member, are dealing with one of these diseases. Now is the time, to shift our focus, and redirect our resources investing in companies focusing on research and development. In some cases, vaccines and cures are on the brink of being discovered, but the lack of financial resources directly dictates the amount allocated to disease recovery and treatment. And If elected, I will pass bills to aid in the research and development of diseases and to ensure our focus is on developing vaccines, cures, and treatments…” Along the campaign trail: While caravanning through various states, Mr. Smith, receives a call from his wife that the results were in, it has been confirmed…his 8 years old son has Lowe syndrome. Now, it was suspected that this was something that his son acquired while they were on a family vacation in a tropical region of SOMEWHERE. A tick bit his son while they were camping. His son visited many doctors and was finally enrolled in a trial for a cure. However, 12 months before Mr. Smith decided to run for president, the trial ended due to lack of funding. He and his family were devastated. And Mr. Smith knew he had to do something.
Back at the campaign office: Mr. Smith and his team were in the process of declaring his platform. Therefore, with the recent outbreaks of Zika in Brazil and the more recent cases confirmed in the US, Senator Smith knew that he could get people to rally behind the need to invest in research and development. That way, the money needed would be resourced back to research facilities, like the one his son was a participant, and they could continue to work on finding a cure. So, Senator Smith and his campaign managers began to devise a plan, and that’s how his platform became one that focuses on a healthier tomorrow for all!! Behind the scenes: Senator Smith had a friend that was doing research in vector-borne diseases for an environmental health company. Over dinner one evening, the friend shared his inside information about the advances that were being made to identify vector borne diseases. The friend shared how there was a device that could potentially be life changing because not only could it detect current vector-borne diseases but also it could potentially detect future diseases. This was the answer to Mr. Smith’s question of how to get people to rally behind the push to do research and development, especially in light of the recent outbreak!
The plan in motion: Mr. Smith met with his friend and told him about his plan to invest in research and how he needed to get people to see this was a crucial topic. He needed people to vote for him. His friend knew the sorrow he was experiencing, and could hear the desperation in his voice so he said he would help him. After all, he thought what harm would it really cause (but he didn’t know to what extremes Mr. Smith would go to get what he wanted). During this meeting, the friend let Mr. Smith in on a secret…He told him that there were other states besides Florida that were under surveillance for infected mosquitoes and that Texas and New Mexico might have the next outbreaks. Later that week, Senator Smith was granted access to data before it was released to the population. Pursuing the lead from his friend, his initial idea took on a new light… He focused on the data from Texas and New Mexico and saw that certain parts of states were under surveillance. He paid close attention to two very popular national parks that were closed, due to this investigation. (Remember, this was information that was confidential and the public would not have access to this information. It was only for security cleared personnel.) “It is not too big of a lie to tell people that their states are infected with arboviruses since it will likely be the case in a short time”, he told his team. So one of his friends who is a computer engineer decided to enter new data in the database so it would appear that Texas and New Mexico were highly infected areas with arboviruses. The aftermath: A few days later, the information was everywhere…from newspapers to appearing as breaking news across television shows; not to mention, it was on every social media outlet that exists. Everyone was talking about the effects of the diseases and how two new states identified regions having infected mosquitoes. Naturally, people were wondering and questioning: What needed to be done to put a stop to the spread? How to protect themselves from getting the illness? What would happen or could be done if they contracted one of these horrific diseases? During a press conference: Senator Smith took full advantage of this opportunity that “fell into his lap” and decided to make several appearances on TV stating, “This is a concerning issue, which shows the importance of allocating a larger portion of federal resources to clinical research and development.” He continues declaring that he wants to give more money to pharmaceutical laboratories and research institutions, obviously to fight diseases transmitted by mosquitoes, but he also stressed how this case shows the importance of being a step ahead in the fight against may other viruses and pathogenic bacteria plaguing our country. “I want us to live in a country that is free of disease and illness…stand with me and HELP ME, HELP YOU fight TOWARDS A HEALTHIER TOMORROW FOR ALL…May God Bless America”, he concludes. What he didn’t anticipate: During Senator Smith’s press report, Mr. and Mrs. Walter, who were living in New Mexico, were following the news and paid close attention to the concern that was being expressed regarding the health of the residents in these states and that their state was likely to be the next place infected by arboviruses. Mrs. Walter was pregnant and she was aware of the consequences Zika virus has on her unborn child. So, Mr. and Mrs. Walter made a life changing decision. Despite the fact that they were a young couple and did not have a lot of money, they decided to move to a state where arboviruses were not reported. They sold their house, packed their things, and moved to Wisconsin. In fact, they were not the only people that made that decision. But this decision wasn’t easy for the Walter’s, nor was it easy for other families. Older people and other families were in no position to leave due to finances and other restraints, so they were forced to stay and hope for the best. They were all in a panicked state of survival. Everything was changing around them. The economy was also impacted by this Zika scare. A number of suppliers refused to travel to these states, therefore, import/export of goods came to a screeching halt. Not to mention, no one was eager to visit states so tourism drastically declined. People were too afraid! The entire vibe of the states was rapidly declining…the BIG cowboy Texas spirit was over and the artists/hippies scenery in New Mexico was not attracting visitors. Since Senator Smith leaked the news about the fabricated data, The Mos(kit)o company appeared to be at fault for developing a system incapable of accurately reporting data. The director of The Mos(kit)o company decided to send a team of experts to set more traps to determine what went wrong. There were traps everywhere. When the results arrived, there was no sign of any infected mosquitos, therefore, no vector-borne viruses in these states. Six months after the initial scare: Senator Smith is now President of the United States and he had to share the news that this was an unwarranted scare…there had been no cases of infections due to vector-borne transmitted diseases in Texas or New Mexico. The few cases that were reported in Florida were all under control and no new cases had been reported. Basically, the country was safe. However, the worse part of what he had to report was a direct reflection of his actions. He had to announce that the country was safe when he knew that all along. He knew he was the cause of everything that happened.