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 Upadhyay, 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.