Silver Human Practices

Choosing a diagnostic track

Attending a Royal Society conference (Synthetic Biology: Does industry get it?) at the start of our project highlighted the diversity of synthetic biology applications, however we were particularly excited by the medical applications. We reviewed the conference for our general university newspaper to explain synthetic biology through examples to a non-science specialist readership. You can read the article here. Understanding of the current medical application of synthetic biology, combined with the results of our initial survey of the public, where more than half of the 200 surveyed wanted a synthetic biology solution for disease diagnosis, guided our initial diagnostics track choice.

Image 1: The team at the Royal Society conference in London

Dialogue with experts, stakeholders and industry informed our decision to focus on acute congenital Chagas disease

Further research focused us on neglected tropical diseases (NTD) because this is where we felt our diagnostic would have most impact (FINDdx, 2015). Chagas disease was chosen after identification of the cruzipain protease as a potential unexplored disease biomarker. Many other parasitic diseases use specific proteases in their infection mechanism giving scope for the development of an adaptable modular diagnostic device with common input and output modules by variable cleavage sequence.

However, literature search and communication with experts researching the use of cruzipain as a drug target exposed the difficulty of quantifying a cruzipain blood concentration due to variable parasite concentration (Emilio Malchiodi, personal communication) making it difficult to ascertain our expected output through modelling. In response to this we designed a split protease based amplification system to increase sensitivity of our detector circuitry.

A PLOS analysis (Albert Picado, 2017) identified a point of care test for congenital Chagas disease as the number one need in Latin America and priority for the world health organisation and ministry of health, despite being lower priority for researchers, therefore we decided to tailor our design to a congenital diagnostic to meet this unmet need (Table 1). Currently there is a 10 month wait for children born to infected mothers for diagnosis, missing the critical window for detection when parasite concentrations are highest a few weeks after birth due to the unsuitability of antibody based rapid diagnostic tests and lack of medical infrastructure (PATH, 2016).

Problem	Our Solution
Lack of medical infrastructure in the worst affected areas compromising follow up and results distribution	A rapid point of care test optimised through modelling
Antibody based tests cannot be used due to presence of maternal antibodies	A non-antibody based test
Blood smear analysis requires training, and PCR tests specialised equipment	A simple test that does not require specialised equipment or medical training using blood clotting as a visible output

Table 1: Evaluation of key problems producing demand for a congenital diagnostic and how our kit seeks to solve these

Surveys to Latin American Teams

3 Latin America teams (AQA_Unesp, Amazonas, and TEC CEM ) kindly translated and distributed surveys to help us understand public perception and acceptance of our diagnostic kit design. 441 people were surveyed in total, and these results informed our decisions to develop a test to be carried out in a medical facility rather than a home test (Figure 1). 28% and 14% of those surveyed were uncomfortable with use of bacteria living in and being used in production of our device, therefore synthetic biology is an acceptable approach.