Team:Nottingham/Human Practices
Human Practices
Follow our Human Practices journey to see how interactions with experts and stakeholders led to the project’s outcomes.
Introduction
We took multiple approaches to consider how best to shape our project so that it is good for the world. We began with a workshop facilitated by our Human Practices supervisor Eleanor Kershaw. During and after this workshop, we discussed possible end users and other stakeholders we thought would have a valuable impact on the direction of our project.
We held several informal discussions with relevant stakeholders, including industry representatives, a medical professional, an academic expert, and a care provider. During these discussions we explored opinions about the application of our project in the real world, technical issues we wanted to address, and social, ethical, and environmental aspects we wanted to consider. From these discussions, we were able to learn more about the context in which our product would be developed and used, and the values and needs of the end users and other stakeholders. We also conducted a literature search to learn about existing uses of biotherapeutics and public perceptions of Genetically Modified Organisms. These exercises shaped our project and our product in a range of ways, making it as theoretically refined as possible and ensuring that it would be responsible and good for the world.
We would like to thank all our stakeholders for taking part in our human practices discussions and for their valuable advice which helped to inform our project.
Our Human Practices work allowed us to consider the risks and benefits of our product, place it in its broader context and consider it from a range of stakeholder perspectives. We put what we learned to use in producing an information leaflet for a general audience: available to view and download on our Education page.
Please click on the drop-down menus below to discover our HP journey.
Integrated Human Practices
CHAIN biotech
Considering what we learned from CHAIN biotech, we changed how we branded and conceived NeuroTone to a biotherapeutic. This had implications not only for branding but also for the potential routes to administration through the use of a pill and the accessibility of NeuroTone through the NHS or as a commercial dietary supplement.
We also have to consider that our organism may be unable to colonise the gut and so we will plan to engineer a strain of NeuroTone able to produce therapeutic levels of D–β–hydroxybutyrate (DBHB) quickly and efficiently.
Because of this, it prompted us to create a dynamic model to simulate the necessary dosing regimen to ensure therapeutic concentrations remain in the patient.
We also learned that we should contact stakeholders in academia and the medicine fields, as these have been invaluable to CHAIN Biotech.
Dr John Morrant
Our meeting with Dr Morrant reinforced our enthusiasm for our project and highlighted the importance of our work.
Patient autonomy is a priority with these treatments, and so we attempted to engineer our biotherapeutic to enable control of dosing regimens.
This meeting also helped us to decide to aim our product at treating susceptible patients in the window of opportunity to delay the outset of symptoms and slowing, the progression of neurodegeneration and not as a cure. Our biotherapeutic could also hopefully be used in conjunction with future diagnostic methods to further delay irreversible damage to neurons.
Oxford University - Professor Kieran Clarke
Following Professor Clarke’s advice, we decided to pursue the production of ketone esters of DBHB and not ketone salts, which may be detrimental to health and offer no benefit in terms of absorption into the blood. This also confirmed that DBHB can reach the brain through the blood, via the gut-brain axis.
We also learned about the potential of NeuroTone to have a wide spectrum of uses in a variety of metabolic functions.
The risk of ketoacidosis in diabetic patients limits the use of NeuroTone and the possibility of ketoacidosis in non-diabetics gave us a broader scope for our project in how we researched the development of a kill switch mechanism in our strain. We will also develop and plan inducible systems of ketone production in our biotherapeutic.
Because of the potential problem of ketoacidosis, we produced a kinetic model to simulate the potential concentrations of DBHB produced by our strain in the gut, to ensure the levels of DBHB produced are not dangerous.
One of our designed pathways, DBHBB utilizes thioesterase II, tesB, from E. coli. We found that this enzyme is also able to act upon the S-isomer of the DBHB precursor, S-3HB-CoA and could therefore result in the formation of the potentially dangerous S form of our ketone. This information, along with modelling, helped us to decide upon proceeding with the DBHBA pathway.
Ms Nicola Cook
Due to what we found out about frequency of dosing regimens being a big problem for carers and patients, we attempted to develop a biotherapeutic which has a longer life in the gut, reducing the dosing regimen frequency if at all possible.
Human Practices
Throughout our project’s lifespan, we spoke with multiple stakeholders from a range of professions and backgrounds in hopes of learning ways we could better shape our project to have a more positive impact on the world. We considered multiple ethical, societal and technical issues associated with our project and with the help from the people who talked with us we gained a better understanding of our project’s context, of the needs, values and priorities of its potential users and other stakeholders, and of the ways in which we could modify our project and our product to better meet those needs, values and priorities.
Wednesday 22nd July 2020
Dr Green and Mr Bradley – INDUSTRY
Background:
Dr Edward Green is a biotech entrepreneur and founder of the microbiome-based therapy company CHAIN Biotech. His company is focused on the development and commercialization of microbial technology to aid in the production and delivery of biotherapeutics.
Mr Ben Bradley is the head of partnerships and licensing at CHAIN Biotech, with areas of expertise in sales and business development skills.
We learned from Dr Green and Mr Bradley that the area of biotherapeutics is new and emerging, with currently no approved products yet. We learned that our project would be considered a biotherapeutic and not a probiotic. Probiotics are traditionally involved in improving nutrition and overall gut health and biotherapeutics involved in specifically targeting a disease, as with NeuroTone.
We also learned that the process of bringing a biotherapeutic (as with any drug) is a very long and expensive process, with no live biotherapeutics currently past phase 3 clinical trials.
The aim of the CHAIN biotech biotherapeutic is not to colonise the gut, but to grow quickly enough and produce enough of the therapeutic molecule to allow the wash out of the engineered organism, resulting in repeated dosing.
Mr Bradley informed us that they have extensively interacted with stakeholders in the form of academic collaborators and industrial partners.
Regarding public perceptions of biotherapeutics, Dr Green and Mr Bradley told us that, in their experience, a patient’s primary concern is the treatment of the disease or condition and less so about how it is achieved.
For access to the in-depth notes for this meeting, please click here.
Wednesday 12th August 2020
Dr Morrant – MEDICAL PROFESSIONAL
Background:
Dr Morrant is a medical professional who has extensive experience in the medical aspects of neurodegeneration, particularly Parkinson’s disease, and was able to provide us with his unique perspective on treating patients with these diseases. Dr Morrant initially trained in cancer medicine, before retraining as a geriatric clinician, with five years specialist training in geriatrics, including neurodegeneration. He held a consultant post from 1990 until his retirement in 2015.
Dr Morrant told us about his experiences and challenges in working as a consultant of geriatric medicine, with an emphasis on Parkinson’s disease. He reinforced the need for new treatments in this area due to the huge impacts these diseases have on a patient’s quality of life and the devastating effects on the family of a patient. We learned that in these cases, patient autonomy is important.
We also learned from Dr Morrant that due to problems with diagnostics, with some symptoms taking more than 20 years to manifest, treatment to delay the outset of neurodegeneration is the main focus in this area.
For access to the in-depth notes for this meeting, please click here.
Tuesday 25th August 2020
Professor Clarke – ACADEMIC EXPERT
Background:
Professor Kieran Clarke is the head of the Cardiac Metabolism Research Group at Oxford University. She conducts research into the effects of diet on energy metabolism in the heart, brain, and skeletal muscle and how this influences physical performance and cognitive function. Professor Clarke is also a founder of the company TΔS, which develops exogenous ketone supplements for human performance and health.
Professor Clark answered our questions on how readily ketones like DBHB are absorbed into the blood. She informed us that ketone esters are safer than ketones conjugated to salts and are also more readily absorbed. Ketone salts are also very understudied and therefore our project should focus on ketone esters. Professor Clarke told us that exogenous ketone esters do not taste good and so a method of delivery in the gut may be preferable.
Professor Clarke also informed us of the wide-ranging positive effects of ketones physiologically on heart health, recovery from physical exercise and even reducing hunger. She also advised that the S isomer of our ketone DBHB, could be detrimental to health and so we should avoid the possibilities of the formation of this potentially dangerous product.
We also learned that uncontrolled production of ketones may result in a condition known as ketoacidosis, which can potentially be a problem for diabetics.
For access to the in-depth notes for this meeting, please click here.
Wednesday 9th SEPTEMBER 2020
Ms Nicola Cook – CARE PROVIDER
Background:
Ms Nicola Cook has extensive experience working in care and provided us with a perspective of those working on the front line of neurodegeneration and what is involved in caring for patients living with neurodegeneration, as well as the everyday lives and needs of people with neurodegeneration living in care homes.
We learned from Ms Cook about the issues of patient compliance with drug regimens, she said that high frequency of dosing can be a problem, with patients refusing dosages.
Ms Cook also reinforced what we had heard from CHAIN Biotech, that public perceptions of a biotherapeutic would be concentrated around the urgent need and desire for effective treatment.
For access to the in-depth notes for this meeting, please click here.
iGEM Nottingham 2020