Team:USP-EEL-Brazil/Human Practices
In order to work on the efficiency of the application and production of antivenom, it's indispensable an approach to mitigate the damage caused to victims of snakebites. However, in a country like Brazil, where public healthcare institutions and services are constantly neglected, this problem requires a wider and more complex solution, which goes beyond synthetic biology techniques. The goal of the Honorato Project was to provide this solution for the community involved. To be able to provide such a solution involving all the different aspects of the problem, we worked together with the community analyzing their constant feedback, so that together we could bring our solutions closer to their real problems.
We chose to take an approach in which we had constant conversations with doctors, nurses, researchers, and the civilian population to maximize our impact on society.
Initially, we had an undeveloped idea, altogether with results from literature reviews, to produce a serum entirely developed by genetically modified organisms for the treatment of ophidic accidents. After consulting some researchers and doctors we realized that our solution using synthetic biology could be much more tangible and that there were many other problems to be solved to improve the lives of these people.
As a consequence of the pandemic context in which the Honorato project was developed, all contacts with society were made virtually. Due also to the difficulties of adaptation during the Covid-19 pandemic, most of the professionals we contacted did not have time for an online interview, and answered us via e-mail.
After the literature review, we proposed the production of a totally recombinant antivenom serum (made from a genetically modified organism), aiming to the end of animal utilization on the production. However, there were still many aspects of the problem of ophidian accidents that we were not able to see just by reviewing the bibliography.
To expand our horizons in this context and to understand what was already being done to prevent the use of animals and also to decrease the number of victims as well as to mitigate the effects on the victims, we consulted three areas of society involved in the problem: health professionals, researchers, and the civil population.
Firstly, we consulted the researchers to validate our proposal to produce a completely recombinant serum.
After Caroline's feedback, we were able to better understand the nature of the snake venom. According to the researchers, snake venom has an extremely complex composition and the protein pattern of these venoms differs greatly on many levels with respect to individual, species, gender, sex, age, geographic location, etc. Despite the complexity of snake venom, the researcher warned us that the creation of a fully recombinant anti-snake serum is not realistic considering the time and resources we had. After clarifying our doubts, Caroline indicated that the production of a single inhibitor for one of the enzyme families of the venom in recombinant form would be a good first step for future research related to the production of a fully recombinant antivenom serum.
After polishing our main idea, we realized that the production of a fully recombinant serum would be infeasible for us as an iGEM team. We then decided to focus our efforts on producing the inhibitor of just one of the enzyme families present in snake venom. We decided to synthesize the γPLI inhibitor, which has inhibitory action against phospholipase A2 enzymes, which are one of the main enzymes that cause tissue necrosis and eventual kidney failure.
We realized that our proposal for a solution of the problem of ophidian accidents in general was getting very far from the reality in which we would effectively improve people's lives. We consulted with some medical specialists and toxicologists to understand more broadly the spheres of the problem so that we could act more effectively.
Dr. Luiz pointed out a fact unknown to us until then, that the toxins from botropic venoms that cause local lesions act very quickly, and when the injured patients arrive at the medical services, they already have tissue damage that may evolve to necrosis. Luiz also told us that the toxins release endogenous mediators from the injured tissue, such as inflammatory mediators, which cause local inflammation. The antivenom (anti-venom serum) neutralizes the toxins of the venom, but it doesn't restore the already present lesions and doesn't neutralize the endogenous factors generated by the poisoning. After consulting Dr. Luiz Roberto, we were able to understand that one of the main problems faced in the treatment of victims of ophidian accidents was the time between the animal bite and the application of the serum.
The professor emphasized that one of the biggest problems is the delay in applying the serum to the victim. This delay can occur for several reasons, such as the lack of availability of the serum in the hospital, the place where the accident occurred, the lack of ambulances, etc. The teacher taught us several techniques for the immediate treatment of accidents, such as tranquilizing the patient, cleaning the site of the bite, leaving the patient at rest, among others. With the teacher's help we were able to gain more knowledge about first aid procedures.
Graduated in Medicine from the Federal University of Espírito Santo and Pathologist by the Medical Residency Program in Pathology at the Federal University of São Paulo, holds a Specialist Title in Pathology from the Brazilian Society of Pathology and the Brazilian Medical Association. Master in Sciences by the Post-Graduation Program of the Department of Pathology of the Federal University of São Paulo.
Carolina alerted us about some practices that can be performed to avoid further complications after the accident, such as limb elevation (most accidents were in the upper or lower limb) to reduce the edema. According to her, this is a criterion for determining the severity of the accident. The greater the edema, the more serious the accident and higher the need for serum. Not controlling the edema may complicate with compartment syndrome. In addition, Carolina warned us about the misinformation spread among some communities suffering from ophidian accidents that elevating the limb would help the poison "spread". This fake news often leads people to tourniquet the affected limb, making the accident victim's condition much worse.
Professor Doctor Bucaretchi is an MS5-1 associate of the Department of Pediatrics at FCM/UNICAMP and Vice-Coordinator of the Center for Information and Toxicological Assistance (CIATox) of Campinas, FCM/ UNICAMP (biennium 2019-2020).
During the phone interview, we could notice Dr. Bucaretchi's extreme concern regarding the delay in serum delivery to the victims, not only because of the lack of time to deliver the serum, but also because of the fact that the serum transportation is too slow to be delivered to the patients.
Dr. Bucaretchi alerted us to the fact that in cases of places farther away from the serum production centers, such as Amazonas, in the extreme north of Brazil, the reception of the serum will suffer complications due to transportation. With this, the doctor indicated that it would be of extreme help to the medical units in the north of the country if there were an intermediate agent to be applied to the injured person, in order to mitigate the immediate effects of the poison in the body, while the appropriate serum is not applied.
All these experts helped us to find again a way to act on the problem in an effective way. We realized, based on feedback from these professionals, that we could act in the time gap between the accident and the application of the serum, providing an intermediate product that would prevent the activity of phospholipases A2 before the victim arrives at the hospital. Together with the professionals Carolina Serino, Dr. Luiz Roberto and Dr. Bucaretchi, we decided to work on the option of producing γPLI inhibitors from GMO's and then making ampoules containing the product available in ambulances and emergency rooms for immediate application. Thus, we could use synthetic biology to significantly decrease the number of cases of loss of limbs and even deaths from venomous animal accidents, since the phospholipase family is present in the venom of almost all venomous animals.
One of the most enriching results of our consultations with the professionals involved in the context of the ophidian accidents was the conclusion that the lack of information regarding first aid procedures was one of the main aggravating factors of the situation of people who suffer from these accidents. Together with these professionals, we were able to identify and propose a solution for this pain involved in the problematic, which led us to engage in the dissemination of correct first aid procedures. For this, we sought contact and space for this disclosure in the main media outlets where we believe the population involved in this problem has access.
To increase the number of viewpoints regarding our work and to see other ways of contributing to the society around us, we made a form for popular consultation. This form garnered hundreds of responses from a wide range of people. We found from one of the questions that 16.1% of the people did not know what a genetically modified organism is.
We note that there is a prejudice against gene editing products through this question in which 3.1% claimed that they would not use a product produced from a genetically modified organism, and 17.61% of the people were in doubt.
We also noticed that a small but significant percentage said they did not find research related to genetic modification useful to society.
To conclude the survey, we asked if people had more knowledge about the subject that would help them better answer the questions above. We noticed that 77.7% of the people who answered yes could give a better opinion if they had more information. We realized the need to contribute to society by providing general knowledge about genetically modified organisms, emphasizing the importance of this type of research for social development and avoiding opinions biased by prejudice. To this end, we created a sequence of dynamic content that was disseminated on social networks in order to bring knowledge to as many people as possible within our capacity.
In order to reduce the worsening of the situation of the injured people who practiced incorrect first aid procedures, we consulted professionals to help us on proposing a solution.
We called Vital Brazil Hospital, Hospital Vital Brazil (HVB), which has been operating for 76 years and is the main health institution in Brazil in the treatment of accidents with venomous animals. An interview was done by phone for approximately one hour. The nurse (Oséias) answered a lot of questions about the daily routine of the professionals who are in the front line on the combat and treatments of snakebite accidents. Oséias also warned us about some factors that helped us expand our understanding of the problem, like some specific reactions caused by the inoculation of the venom of some snake’s genus, like the temporary blindness in victims of rattlesnake bites.
However, the nurse pointed out that one of the main problems is the misinformation, which validates our previous premise.
Following the validation and the advices from Oséias and from other professionals with great understanding of the problem, like the pharmacists Paulo Roberto and Laura Prodomo, we decided to make a plan of awareness in order to get to the biggest possible number of people, getting in touch and searching for space in all medias channels.
The popular form was developed so we could scan how synthetic biology is being perceived by society around us. With the results from the form it was possible to comprehend more about the acceptance level of this new science, as well as the general understanding of its impacts. These feedbacks helped us to highlight the seriousness of the misinformation about these subjects.
With the goal of reducing this problem, we decided to develop some digital content that would make communication with society beyond our university’s gates possible, introducing them to the world of this science area. We chose the digital approach because of all the mobility limitations during the pandemic and also because we believe that currently the digital world is the best way to connect with the majority of the Brazilian population.
In order to minimize the problem of popular misinformation about first-aid procedures, we reached out to a lot of digital media channels since the pandemic stopped us from making a significant disclosure on the streets of our city.
We had the opportunity to share the correct first-aid procedures on “TV Metropolitana”, which is a wide-ranging communication’s channel in the countryside of the state of São Paulo, the place with the outbreaks of snakebites in the state.
We had the opportunity to share about our project and to raise awareness about the problem at the newspaper of the University of São Paulo, the biggest university in Latin America.
We were invited to participate in “Mamutes na Ciência” which is a podcast focused on scientific dissemination. There we brought in an open and dynamic way the synthetic biology agenda for an audience not very familiar with the theme. We took advantage of this opportunity to talk about the problems related to ophidian accidents.
Misinformation is one of the biggest problems faced by Brazil in this century. We’re living at a time in which denialism and aversion to education and information are a reality in a huge part of our society.
Thinking about this scenario and encouraged by the information obtained through a popular consultation form, we developed a full content of scientific dissemination focused on synthetic biology, contributing to the fight against misinformation in our society.
We worked on a sequence of didactic videos with accessible language explaining some synthetic biology’s concepts, some projects that had a high impact on society and also the potential of this science area.
Hospital Vital Brazil
Butantan Institute