Team:IISER-Tirupati India/Human Practices
OviCloak, throughout its journey, endeavoured to be a people’s project. From brainstorming to implementation, we involved our stakeholders. Our vision was to make our stakeholders understand the design of the project, know their desire and close the loop between both.
OviCloak being a proposed synthetic biology alternative for existing contraceptives, demands thoughtfulness about whether it is responsible and good for the world. Through our human practices, we tried to achieve this via :
Our team initiated thoughtfulness from the brainstorming sessions in which the problems we wished to address spanned from poverty to plastic pollution. We came up with solutions using synthetic biology to tackle these problems. However, we also verified if our proposed synthetic biology methods are better than the existing solutions/proposed solutions to these problems.
“About 22.2 million unintended pregnancies in 43 developing countries are due to contraceptive failure. -WHO”
“Modern contraceptive prevalence among Married women of reproductive age (MWRA) increased worldwide between 2000 and 2019 by 2.1% points from 55.0% (95% UI 53.7%–56.3%) to 57.1% (95% UI 54.6%–59.5%)1. Reasons for this slow increase include: limited choice of methods; limited access to services, particularly among young, poorer and unmarried people; fear or experience of side-effects. -WHO“
“In India, an irreversible procedure like female sterilization is preferable for more than 75% of cases that take away the individual’s right to plan families. -FP2020 ”
This caught our attention! We recognised that being an integral part of society, the lack of a sustainable & empowering contraceptive affects the safety of individuals globally & thus this issue demands the centre stage. We wished to bestow an effective and safe alternative to the 933 million contraceptive users through synthetic biology.
Thus, our journey towards OviCloak started.
Stakeholder analysis
The analysis section of The iGEMers Guide to the Future helped us contemplate the values that we want to embed for the potential users of OviCloak through the stakeholder/value matrix. Health (Safety), Environmental Safety, Autonomy/individual choice are values we wish to embed and as well as fulfilled by OviCloak.
Market Survey
Further, to understand what needs and values are our stakeholders looking forth in our project and to evaluate whether the values fulfilled OviCloak meet their preferences, we decided to conduct a market survey. We found that a significant fraction of the contraceptive users were seen to experience side effects, hence our vision of prioritising health safety will be endorsed by our stakeholders. Least to no side effects, environmental safety, reversibility and long-term action of the contraceptive were some of the attributes respondents felt important for their contraceptive.These are values OviCloak wishes to fulfil.
Thus, we felt that OviCloak would benefit the contraceptive users.
Read a detailed analysis of Markey survey here
Meeting with stakeholders
Through meetings with Stakeholders, We could understand the importance of some values which were left unaddressed.
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SWOT Analysis
We performed a SWOT analysis to reflect the strength, weaknesses, opportunities and threats of our project.
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Stakeholder identification
Identifying the stakeholders was the first step in comprehending the importance of the team and project being safe and responsible.
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SWOT Analysis
From SWOT analysis, we understood the threats posed by our projects such as lack of awareness about contraception in civilians, horizontal gene transfer or biosafety and lack of funding.
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The values and risks workshop
We attended the values and risks workshop conducted by iGEM Ambassadors.
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Responsible Research
Our team strived to be responsible and safe throughout the project inside and outside labs by adhering to lab rules and COVID-19 protocols. Read more in Safety.
We understood that our project has a great potential to impact the world outside the lab. For this, we strived to set up a two-way dialogue between us and the world.
Our aim was to :
- Learn about the world outside the lab
- Integrate the learning into our project.
This was achieved by a strategic move by our team as the following :
Stakeholder Identification
Stakeholder identification which was done as a part of our reflection was the cornerstone for responsiveness.
Reaching out
Finding out the identified stakeholders and experts were challenging. The ongoing pandemic necessitated doing our human practices responsibly with limited personal contact.
With constant online search, we could find contacts (Mail Id, contact number) of experts. Social Platforms such as LinkedIn and Instagram helped us a lot in this step. Some experts were kind enough to introduce us to some other experts and stakeholders.
Engaging with stakeholders was still a challenge due to COVID-19 restrictions, so we thought why not start from our home. We conducted In-Depth Interviews with our family members of 18+ age, thereby initiating the conversation around sexual and reproductive health from our homes.
Engaging with stakeholders and experts.
We opted for In-Depth Interviews for one-on-one engagement with our stakeholders and experts. While surveys came to the rescue to engage with a large population of stakeholders.
We strived to adhere to all COVID-19 regulations as well as ethics while doing human research. Read more in Safety.
Closing the loop
Analysis
We analysed the IDIs and Surveys. Surveys were analysed and infographics were made for better representation.
Integrating
Closing the loop between what is designed and desired is at the heart of our human practices. We strived to do that through :
- Discussing the feedback and selecting the relevant ones on the basis of values chosen.
- Conducting literature surveys or testing through mathematical modelling.
- Engaging with the stakeholder to get feedback on integration.
This is iterated throughout our project. This feedback and integration helped us build a people’s project.
INTEGRATED HUMAN PRACTICES
How iHP moulded OviCloak
Our stakeholders played an unequivocal role in the shaping of OviCloak. Here, we highlight how our Human Practices informed our ethical, technical, safety and communication decisions and closed the loop between what is desired and designed.
To know details, see timeline below
Feasibility and Desirability
In our Initial social science research, we understood the need for a novel contraceptive.
- In addition to this, we conducted In-Depth Interviews to learn about the general opinion of people on existing contraceptives and their perspective on the need for new contraceptives. We also wanted to know about people’s views on OviCloak and the usage of a GMO for contraception. Keeping in view the COVID-19 restrictions, we conducted In-Depth Interviews with our family members and friends of 18+ age. Since our team members are from different parts of India, we could ensure the diversity of the respondents by conducting this with people at various locations in India.
See the detailed analysis of IDI here.
- Through reflection, we wished to embed safety and autonomy into our project. Interaction with stakeholders helped us understand the other values we left out and prioritise the values.
Read more in Reflection to know the needs or values we prioritized in our project’s design and the compromises made by us.
Broadening the spectrum of End-users
Iterative feedback from our stakeholders and their integration helped us make the project good for the world, especially for the communities left uncared for.
Dr Madhulika Pathak, a doctoral researcher with a demonstrated history of working in academic research about mammalian embryo development, helped us realize that our approach to contraception has been limited to the ideal reproductive tract anatomy and hormonal levels of "women". We were asked whether our contraceptive caters to the needs of individuals with Poly Cystic Ovarian Syndrome. We set out to improve upon this fact by connecting with another expert, Dr Prameela Menon- A gynecologist. She gave us direction in the improvement needed in the design.
Frequent discussions with our Institute's LGBTQIA+ awareness club, "Rainbows of IISER Tirupati", helped us understand the importance of individuals belonging to the transmasculine and intersex individuals as our stakeholders. This inspired us to call OviCloak a "novel female contraceptive" instead of a "novel contraceptive for women as "woman" only refers to a particular gender of the gender binary.
In the meeting with the NGO "Sex Education for India", we understood the need for a more inclusive term as the term "female" is not inclusive of individuals belonging to the "transmasculine" and "intersex" communities who don't identify with the words "male" and "female". After brainstorming, we came up with a more inclusive title, 'A novel contraceptive for Uterus owners'
In our initial quest to broaden our end-user spectrum, we came across conditions like Congenital adrenal hyperplasia (CAH), Turner Syndrome, and people from a transmasculine spectrum who could be our potential stakeholders. In the meeting with Dr Frances Grimstad, she pointed out another condition called Cloacal Exstrophy, which can be considered.
Thus, OviCloak became a contraceptive for all uterus owners.
Design of Genetic Circuit
Initially, we had a progesterone-induced approach for regulating ovastacin production. In the meeting with Dr Satish Gupta, an Emeritus Scientist at the National Institute of Immunology, he pointed out the importance of sensitivity of the transcription factor, SRTF1, for efficient regulation during minimal Progesterone production. Hence, we set out to look for alternative sensing molecules as we found SRTF1 has less sensitivity to sense the minimal concentration of Progesterone during the onset of ovulation[2].
Meanwhile, we met with Dr Prameela Menon, a gynaecologist. She raised the concern regarding the late expression of ovastacin, as the fertilisation window is very short. So, we set out to look into an alternative design for the regulation of ovastacin.
Eventually, we came up with Progesterone repressed regulatory systems for ovastacin production, which overcame the previous concerns.
Safety
The prime value we wished to embed in OviCloak was Safety, which is not complete without Biosafety. Hence, we gave importance to the kill switch module of our project and most importantly, we made a constant effort to get feedback and integrate them into our kill switches.
Initially, our project was designed to have a kill switch for reversibility which was thought to prevent the unintentional release of genetically modified commensal. But, Dr Gupta raised the concern of dissemination of genetically modified commensal into the environment. So, we reflected on the scenarios where engineered bacteria can escape the fallopian tube. This led to thorough literature surveys [3][4] and designing a kill switch for biosafety.
In the meeting with Dr Pathak , she raised the concern of leaky expression in the proposed model of the kill switches. We set out to look for a better design with non-leaky expressions. Eventually, we decided to use the toxin-antitoxin system for the kill switch as it seems to control leaky expression [5].
Once the genetic circuit design for both the kill switches was ready, we met with Dr Brenda Wilson, a microbiologist from the University of Illinois. Dr Wilson pointed out the possibility of a toxic shock from the endotoxins released on the activation of the kill switch. She suggested alternatives to the kill switch, such as using antibiotics and a replication inhibitor called Psoralen, which can prevent the growth of bacteria instead of killing them. This was indeed a matter of thought which we wish to incorporate into our kill switch in the future.
Bringing OviCloak into Real world
Our meetings with experts helped us understand the challenges and scope of improvement to bring OviCloak to the real world.
Delivery System
In the initial months of our project, we thought of improvising an IUD to deliver the genetically engineered bacteria into the fallopian tube. On reflection, we didn’t want to develop a device that would stay inside the uterus of the user.
We continued our quest for an alternative, and it was meeting with Prof Debjani Paul, an Associate professor in the Department of Biosciences and Bioengineering at IIT Bombay that we realised the challenges of considered alternatives like direct delivery, two fluid delivery and injecting into the Ostia. Dr Prameela and Dr Paul suggested that using an existing method with minimum changes is the best solution.
In the meeting with Dr Sidra Khot, an IVF expert we learned about hysterosalpingogram, Hysteroscopy and catheters. We knocked out hysterosalpingogram as it is only familiar to fertility experts leading to reduced accessibility. Similarly, Catheter needs a well-trained gynaecologist for its operation.
Thus, by integrating the feedback from the stakeholders mentioned above, we decided to deliver the genetically modified bacteria with a technique called Hysteroscopy, as it is more accessible.
Dr Brenda and Ms Nalini raised concerns regarding the user-friendliness of our delivery system. Finding a delivery system, which can deliver the genetically engineered bacteria in a more user-friendly way is our future prospective.
Implementation
Dr Praveen Vemula, a translational researcher, made us understand the importance of proof of concept for each aspect of our project. We were advised to go through safety regulatory guidelines and plan the proof of concept accordingly for biosafety.
Dr Diana Blithe, The Chief of Contraceptive Development Program at the National Institutes of Health, U.S. Department of Health and Human Services and the Co-director of the Contraceptive Clinical Trials Network helped us understand the steps in pre-clinical and clinical trials which OviCloak have to undergo before potential approval by Regulatory boards.
To figure out the possibilities of a business model, we met Dr Deepika Upadhyaya, an associate professor at the Department of Management Studies at Maharshi Dayanand Saraswati University and brainstormed the end-users. This led us to conclude that our product could be better marketed to an urban/suburban population and subsequently cost subsidised to cater to rural populations’ needs.
We met with Six experts from FHI 360, a nonprofit human development organization with a history in family planning and reproductive health projects. They gave us invaluable insights into the manufacturing and post-production processes, including packaging and delivery. We got to know about the procedures OviCloak, undergoes before it gets subsidised by the Governmental Organisation or marketed. They raised concern regarding maintaining cold-chain during delivery, as it is a crucial factor during procurement by agencies
Read more on our vision about bringing OviCloak into the real world in Implementation.
Communication
The stakeholder engagement was the inspiration behind our educational activities related to sexual and reproductive well-being.
Meeting Ms Kathy Walkiling was eye-opening as her experience of launching Ecofemme, a menstrual hygiene start-up, made us understand that the stigma surrounding the use of sexual and reproductive health products can be a challenge to implement OviCloak. Thus, we realized the importance of spreading awareness about sexual and reproductive health along with developing a novel contraceptive. This led us to collect data regarding the status of awareness on Reproductive Health and Rights as well as Conducting Sexual and Reproductive Health awareness sessions such as webinars, social media posts and virtual art exhibitions.
We met with Mr Kaustubh Jogelkhar, who is the senior counsellor at an NGO called Pankh that educates young minds about sexual and Reproductive health. The most important takeaway message from him was to deliver the content that fits the short attention span of the current generation. Hence, we explored the possibility of reaching the audience through social media platforms like Instagram reels and Instagram Live sessions.
Ms Sophie Wang, a communicator from the online magazine ‘Biorad’ made us understand the impact of Interactive Zines through her work..This Idea amazed us all, as this perfectly fits into the iGEM’s human practices strategy, setting a two-way dialogue.
Integrated Human Practices Timeline
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References
- Lund University. (2016, March 4). Estrogen in birth control pills has a negative impact on fish. ScienceDaily
- Grazon, C., Baer, R. C., Kuzmanović, U., Nguyen, T., Chen, M., Zamani, M., ... & Galagan, J. E. (2020). A progesterone biosensor derived from microbial screening. Nature communications, 11(1), 1-10
- Patiño, R., Bolamba, D., Thomas, P., & Kumakura, N. (2005). Effects of external pH on hormonally regulated ovarian follicle maturation and ovulation in Atlantic croaker.General and comparative endocrinology, 141(2), 126–134. https://doi.org/10.1016/j.ygcen.2004.12.006
- Shi, D., Komatsu, K., Hirao, M., Toyooka, Y., Koyama, H., Tissir, F., ... & Fujimori, T. (2014). Celsr1 is required for the generation of polarity at multiple levels of the mouse oviduct. Development, 141(23), 4558-4568.
- Brantl, S., & Müller, P. (2019). Toxin Antitoxin Systems in Bacillus subtilis. Toxins, 11(5), 262. https://doi.org/10.3390/toxins11050262
- https://live.flatland.agency/12290417/rathenau-igem/
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