Team:Oxford/Human Practices
Human Practices
Overview
An important aspect of synthetic biology is the consideration of how the technology has applications in the context of the wider society. We believe that collaborating with scientists, clinicians, social scientists, patients and the general public is essential to ensuring that our product benefits society. Our approach to human practices involved working with professionals, patients and the public to understand their opinions about various aspects of our project, and using this feedback to alter the design of our project and tailor our educational outreach activities.
The focus of our work on human practices was to integrate four major themes:
- Applied Design
Our approach to applied design involved creating surveys and interviewing patients to analyse the unmet patient needs and the most important issues that require addressing to improve patients’ quality of life. Regular conversations with patients, as well as professionals experienced in law, manufacture and clinical delivery of therapeutics, enabled our design to continually evolve in light of this feedback.
- Public Engagement and Outreach
As a field still in its infancy, public knowledge of synthetic biology is limited and is often viewed with scepticism. As a result, public acceptance of genetically engineered therapeutics will be restricted by public knowledge unless educational resources are provided. The provision of summer school classes, public outreach events, online resources and a long-term public education plan were parts of our public outreach efforts. Our public engagement was integrated with our work covering applied design, as we remained open to feedback and used guidance from the public to shape our product design.
- Entrepreneurship
Our focus on entrepreneurship was a way of understanding how our therapeutic could be transitioned from the lab into the real world. We interviewed IBD patients and other key decision makers to determine the best value proposition. We surveyed the public about their preferences for potential products, and considered patents and regulatory procedures governing how our therapeutic can be taken into market.
- Safety
Safety is an essential consideration for the design of any genetically modified organism, particularly those used as medications. Discussions with clinicians and researchers, as well as some of the questions raised by patients and public we spoke to, encouraged us to make safety a key focus of our integrated human practices. Taking on the advice of professionals, we developed different designs of a kill switch and modeled the safety risks associated with our design.
Detailed information about our work centred around each of the four themes can be found on the respective pages of our wiki.
Overview of Integrated Human Practices
Our philosophy regarding human practices was to ensure a reciprocal relationship between our team and society, ensuring that we remain open to feedback from the public, patients and professionals. Our human practices work involved the education of the wider public about our project ideas and the broader applications of synthetic biology, as well as discussions and interviews to understand society’s opinions of our project. We acted upon the feedback we received, meaning that our project continually evolved in light of the public’s input. An important focus of our work was to ensure that ‘society’ encompassed the broadest range of individuals, so we engaged with clinicians, researchers, professionals involved in the legal and business side of drug development, patients, students and the lay public.
In this manner, our vision and plans for human practices were altered throughout the course of the project. The timeline below summarises our work for human practices and demonstrates how engaging with different individuals prompted us to take alternative pathways in the project, both in terms of human practices and the design of our therapeutic.
Timeline of Integrated Human Practices Work
First Survey
When we were first coming up with a project we involved the public by reaching out from our social media with a survey. We assessed the general awareness of genetic engineering and asked which real-world issue they believed should be the focus of our project.
The overwhelming majority of survey participants picked therapeutics as an area of priority, this influenced the development of our project into a therapeutic based idea from our initial ideas.
Patient Consultation
After deciding on which issue we should work on we came across autoimmune diseases and believed current treatments are not sufficient. To ensure this was the case we consulted patients and clinicians and asked specific problems that result from the disease and current treatments
Patient Interviews
Engaging with patients - the end-users of our product - was important for understanding the unmet patient needs that we are aiming to rectify. This gave us an insight into what features will be important in the design of the product, although it became apparent that it would be beneficial to conduct one-to-one patient interviews to gain a greater understanding of the specific impact of the disease on patients’ quality of life. Taking on advice from clinicians, as well as the apparent range of symptoms associated with different autoimmune diseases, we chose to focus our product on the treatment of IBD. As a widely accepted method of “gaining insight into people’s feelings, understanding and perceptions”, one-to-one interviews played an important role in understanding the issues that our product must rectify to have the most significant benefit to patients’ quality of life.
We have gone into more depth on the conduction and results of patient interviews in our product design section. The results clearly show current treatments are not sufficient. The main points we took away from the interviews are that patients seek treatments that reduce flare-ups, have fewer long term side effects and less of an impact on social life. This greatly aided in the development of our device.
Autoimmune Disease Survey
We sent out a survey for patients with autoimmune diseases in order get a better idea of what patients would like from a treatment. We received 48 responses from members of the public suffering from autoimmune diseases from a range of age groups. The responses gave us a greater understanding of the current treatments, the problems with them and what patients would like from a treatment. We were astounded by the positivity towards GE and for our project. There is a great deal of belief from the public in the potential of GE in medicine.
They survey told us the public wanted a treatment that treats “a condition at its source rather than masking symptoms.” that was also “less invasive and less dangerous”. They also showed support of a device that was able to provide personalised doses according to the patient. This led to the initial design of our treatment.
Developing our design
Having received feedback from patients we learnt what was sought after in a novel treatment. We then reached out to specialists to comment on the initial design of our device in order to maximise the efficacy of our treatment based on current knowledge on the immune system and IBD.
Professor Simon Travis We got in contact with Professor Travis, Professor of Clinical Gastroenterology, who has been the President of the European Crohn’s and Colitis Organisation (ECCO) and an elected Member of the International Organisation of Inflammatory Bowel Disease. As well as gaining an insight into the current problems with treatments and what a doctor would like out of a new treatment, Professor Travis was pivotal in the development of our product from a general treatment of autoimmune diseases to focusing on IBD. A more specific focus while developing the treatment allowed us to produce a device that has a greater focus on gastrointestinal inflammation. A probiotic has a very localised effect in the intestine, this means it will have a greater and more immediate impact on inflammation occurring in the gut. This is why we have specifically chosen Crohn’s disease and Ulcerative Colitis with the belief that our treatment will have the greatest improvement over current therapies.
Safety
Patient interviews, surveys and consultations with specialists highlighted the need to incorporate a biosafety mechanism into our device. We responded to this feedback by designing, synthesising and characterising a single component kill switch. More can be read about this on improvement of a part and our safety pages. On top of this in order to encourage the use of GM probiotic treatments for a greater range of conditions.
Regulation
Dr Michael Morrison - Centre for Health, Law and Emerging Technologies (HELEX)
Over the summer we met with Dr Morrison on multiple occasions to discuss the law and regulations that would be relevant to the development of our product. He gave us guidance on the various regulations that would govern how our product could be used clinically, and gave us an understanding of the processes required during clinical trials. The work with Dr Morrison was incredibly important in the creation of our proposal on the safety of GM probiotics, a long-term public education plan, and theoretical plans for completing clinical trials and the manufacture of our probiotic. Dr Morrison was also able to guide us towards information on a range of gene therapy case studies as mentioned on product design. He also put us in contact with Cell and Gene Therapy Catapult.
Cell and Gene Therapy Catapult
Catapult is a centre to help and encourage growth of cell and gene therapies by aiding with regulation, product testing, logistics, manufacture and business advice.
We met with Daniel Rabbie, the Regulatory Affairs Manager, and Ryan McCoy, the Senior Process Development Scientist to discuss how our product fits in with current government regulations and how we can take it from the lab to the patients. We discussed the differences in regulation in different therapies, the organisations available to speed up the process of getting the treatment from the lab to the patient, current therapies, and considerations involving logistics and manufacture.
In order to understand how to navigate the laws and regulations in different countries, we created a document to investigate the various regulatory bodies
If we are to start providing this therapeutic to children, we would need to carry out pediatric trials, which carry a host of new regulations (in note format)
ATMP Classification
The classification of treatment is important in determining the right regulatory bodies you must go through. Our treatment would likely count as an Advanced Therapy Medicinal Product (ATMP) according to the European Medical Agency (EMA). The EMA’s Committee for Advanced Therapies (CAT) advise on whether a treatment would be considered an ATMP and what type it would be, such as a cell or gene therapy. We found a previous therapy involving modified Lactococcus lactis engineered to produce anti-TNF alpha antibody fragment for the treatment of Ulcerative Colitis. From this we can assume our treatment would be classified as a gene therapy medicinal product. To confirm this we have submitted an application for ATMP classification with CAT from the EMA which we are waiting to hear back from. More information on reasons for this classification as well as our submitted form can be found on the product design section. We believe the form can be used as a reference for others seeking classification of new types of medicinal therapy in the EU.
Delivery
As a new type of medicinal product it is also important to determine how we can successfully deliver the device to the gut.We had been considering how our product would be delivered to the gut from early on the project. Our aim was to develop a 'friendlier' treatment but it is important to consider the possibilities for a probiotic in order to maximise the likelihood of colonisation in the gut. Further details on delivery can be found in product design.
Dr Nick Thomson - Quadrum Institute, Norwich
Dr Thomson gave us an invaluable insight into the delivery mechanisms of probiotics and how to ensure the probiotic bacteria establish a niche within the microbiome. He gave us guidance on the types of strain to use in the probiotic product, introducing us to studies demonstrating that VSL#3 (a polybiotic solution containing many different probiotic bacterial strains) can be taken orally to improve Crohn’s disease. This gave us a useful direction for our research into probiotic strains and probiotic delivery. He also gave us useful ideas for areas of further research to test our product, such as using a model colon - with varying concentrations of oxygen and carbon, to test the bacteria in environments similar to the natural colon. He also praised our kill switch designs, again highlighting the importance of addressing the safety concerns associated with GM probioitcs.
Dr Chris Barnes - Department of Cell and Environmental Biology, UCL
Dr Barnes provided useful information about the colonisation of probiotic bacteria in the gut, demonstrating the importance of choosing the right chassis. He also suggested that we should focus on controlling the bacterial population size and should consider quorum sensing as a method of ensuring that the population remains at a constant level.
Psychological Impact
Our initial survey highlighted the importance of the delivery method in a psychological way as well as functionally. Patients told us they would like a treatment which is simpler than their current treatments especially compared to having to be on an IV. We were told that the patients found the use of needles for biological treatments can scary especially for younger patients. We were also informed how these psychological considerations are particularly important for chronic conditions compared to other conditions. For this reason, we decided to place a greater focus on the method of treatment and try to ensure we come up with the easiest and safest method for the patient.
Dr Sam Parsons - Oxford Centre for Emotions and Affective Neuroscience
Dr Parsons is a psychologist and he shared information about the psychological impact of autoimmune conditions, including the psychological impact of chronic pain, isolation, stigma, and phobias of hospitals/needles. This enabled us to understand further complications of autoimmune diseases, and encouraged us to choose an oral form of probiotic delivery in order to create a minimally invasive, easily administered treatment.
Surveys
As well as consultation with specialists we conducted surveys with the public and members of the Oxford Biochemistry Department to gain an insight of how people would like to have treatments administered and why. We initially received support for packaging the product in a yoghurt in our first survey. We conducted two surveys with the aim of finding the preferred delivery method of the public. Our first survey was conducted at ‘Meet the Experts’ at Oxford University Museum of Natural History and our second was sent out to members of the Oxford Biochemistry department. The first was at an event for children and families whilst the second was completed by specialists with a higher level of understanding of GMOs.
The most favoured method in the Natural History Museum survey was the yoghurt drink. Injections received many votes but only from children under 12 either because of association of injections with effectiveness or because they found the idea of injections exciting.
From our survey in the department we were able to ask a significantly larger group of people their opinion as well as receiving reasons for their choices. Capsules resulted as the favoured method from this survey. Yoghurts received votes due to their convenience but capsules was preferred for the same reason as well as its establishment in medicine, ease of storage and transport, and its superior half-life.
References
| Reference |
|---|
| EMA (2018). [online] Available at: http://www.ema.europa.eu [Accessed 11 Sep. 2018]. |
| Wikipedia (2018). Pharmaceuticals and Medical Devices Agency. [online] Available at: https://en.wikipedia.org/wiki/Pharmaceuticals_and_Medical_Devices_Agency [Accessed 11 Sep. 2018]. |
| FDA (2018). U S Food and Drug Administration Home Page. [online] Available at: https://www.fda.gov/default.htm [Accessed 11 Sep. 2018]. |
| PMDA (2018). Services of PMDA | Pharmaceuticals and Medical Devices Agency. [online] Available at: https://www.pmda.go.jp/english/about-pmda/outline/0006.html [Accessed 11 Sep. 2018]. |
| CDSCO. (2018). Central Drugs Standard Control Organization. [online] Available at: http://cdsco.nic.in/forms/Default.aspx [Accessed 11 Sep. 2018]. |
| Mankar, Someshwar & D Gholap, V & P Zende, T & S Dighe, R. (2014). DRUG REGULATORY AGENCIES IN INDIA, USA, EUROPE AND JAPAN-A REVIEW. INTERNATIONAL JOURNAL OF INSTITUTIONAL PHARMACY AND LIFE SCIENCES. 4. 2249-6807. |
| Slingerland AE, Schwabkey Z, Wiesnoski DH, Jenq RR. Clinical Evidence for the Microbiome in Inflammatory Diseases. Frontiers in Immunology. 2017;8:400. |