Integrated Human Practices | Sydney_Australia

Our Project in Context

Dr. Clare Skinner, Emergency Physician Sydney

We spoke over zoom with Dr. Clare Skinner, a local specialist emergency physician with over two decades of experience as a clinician, educator and advocate in the emergency medicine and public health space. Our conversation centred around the applicability and implications of Point of Care serology testing, which is a major general area we hope our foundational technology can be applied to. We were able to gain very valuable insight from Clare, that we have broken down into the following categories:

Features of a Useful Point of Care Serology-based Test

“There’s no point in diagnosing something for diagnoses sake, [it is] only useful if you can do targeted treatment.”

One idea Clare stressed right from the get go was that not all diagnostic tests are useful - just because you can find something out, does not make a specific diagnosis clinically or socially (in a public health context) valuable. The key idea here is that, clinically, the result of the test must change the course of treatment or the actions of the clinicians or patients in a meaningful way. For example, discussing in the context of COVID-19 (our main proposed implementation, due to public awareness, and existing models of care), Clare mentioned that at the moment in the Emergency Department, a Rapid Antigen Test is not so useful as if someone comes into the clinic with associated symptoms, a clinician is going to treat them as if they have COVID-19 anyway. However, if a new highly virulent strain was to emerge then their utility would increase, and it may be useful to be able to differentiate between a less/more life-threatening strains for the purposes of triage and management.

Through our discussion together, several themes kept emerging that have been condensed to a list of general contexts where a Point of Care Serology-based Test is useful:

Where a targeted treatment is available.
Where surveillance can lead to changes in Public Health Measures to be implemented.
Where there may be barriers to access, or the test targets a population subset that is less likely to visit the doctor.
When the diagnosis is time sensitive. Current methods may be too slow, or the illness may progress rapidly, or if treating early is crucial.
When a diagnosis of a common condition can rule out other more severe conditions.
When symptoms are nonspecific/misleading or the patient is unable to communicate symptoms with ease (eg: infants and young children).
When hospitals need to control spread of an infection through the ward or building.

How We Responded

Given the context of healthcare spending at a record high (NSW Health 2022), our team wants to ensure that our proposed implementation is a test that would add value to the healthcare system, i.e. a test that addresses one or more of the above contexts, and not be a source of wasted money. While Clare affirmed that using our DNA shuffling methods to be able to predict antigenic shift would be useful, the limited utility of the current Rapid Flow Assay in the clinic was not something we had fully considered. The ability to differentiate between a highly virulent strain (if it were to emerge), and one that may not be as life-threatening in one test, was indicated to be more useful than what there currently is.

Our response was to look into multiplexing on a single test. From our original fuGFP, we generated 4 other free-use fluorescent proteins that differ in the Ex/Em spectra. We attached these to our cellulose-binding domains as well, and confirmed they retained the ability to fluoresce, bind to cellulose, and be eluted from cellulose. This enables a test to be created with multiple test lanes that could show up in different fluorescent wavelengths to distinguish between strains of a disease.

An Expanded Range of Applications

While testing for SARS-CoV-2 was the major focal example application we had been thinking of, due to its recent spotlight in the public consciousness, our meeting with Clare revealed many more applications that share the characteristics of the above contexts, and also fleshed out others that we had thought of but were lacking in detail.While testing for SARS-CoV-2 was the major focal example application we had been thinking of, due to its recent spotlight in the public consciousness, our meeting with Clare revealed many more applications that share the characteristics of the above contexts, and also fleshed out others that we had thought of but were lacking in detail.

We asked Clare what specific other infectious diseases or clinical conditions she would like to see Point of Care serology-based testing for. Three main contexts emerged that we would like to highlight, in addition to a host of others (listed below).

Meningococcus

This disease has a few critical features that mean a POC Serology-based test may have the ability to improve outcomes:

Hard to diagnose, people come in non-specifically sick
Rapidly progresses towards severe outcomes
Risk groups include infants, young children and teenagers:
- Infants and young children may not be able to articulate their symptoms
- Teenagers are a group who are less likely to seek medical attention, and immunity from vaccinations wear off at this age
Currently diagnosed by lumbar puncture - this is a semi-invasive operation that people can be put off by

Group A Streptococcus

"First Nations First: If what you’re developing wouldn’t work well in Hermannsburg, Northern Territory, then it doesn’t work at all."

In this case, there is a particular equity focus, which we will touch on more later on. In the local Australian context, Acute Rheumatic Fever (ARF) caused by group A streptococcus infection disproportionately affect Indigenous Australians, making up 95% of all Australian cases from 2015-2019, despite only representing around 4% of the population (ABS 2021; AIHW 2021). Indigenous Australians face added barriers to accessing healthcare, such as the lack of culturally competent healthcare. Point of Care testing has been shown to be effective in remote Indigenous communities in Australia during the COVID-19 pandemic (Hengel et al. 2021). A test for Group A Strep that could be administered at point of care or self-administered such as the COVID-19 rapid flow assays may help to decrease the barriers to accessing medical assistance.

Paediatric Rashes and Whooping Cough

Whooping Cough:

Can cause a backlog due to a non-specific diagnosis (coughing until you vomit), obscuring genuine cases
Diagnostic clues come from history, which young kids cannot provide

A highly specific test would be most beneficial in this case, as a screening mechanism in hospitals.

Paediatric Rashes:

A targeted treatment is available
Young children and infants may not be able to give complete history
Infected individuals need to isolated with other individuals with the same infection

Others:

Dental context: Dental Abscesses, model is already Point of Care
Agricultural context
STIs:
- Associated shame may prevent individuals from seeking care, so mail-out at home testing could be useful.
Screening for Antibiotic Resistance:
- Current methods require overnight or at times multi-day cultures which at times takes too long to be relevant to treatment

How We Responded

This conversation affirmed what we already knew was one strength of our project - the wide potential for applications - and generated excitement and more routes for research. We are cautious not to hinge on the testimony of n = 1, and so we took the ideas and branched off into our own literature deep dives. We’ve adapted our proposed implementation page to reflect these new ideas, a change that can be tracked back through the record by comparing it to our project proposal and promotional video.

Potential Issues in Implementation

“Any health tool you create will be overused by the healthy, worried, well and underused by people who actually need it.”

While the above gives an optimistic outlook, implementing such tests in reality is never that simple, something Clare made sure to stress to us. Some key issues that were brought up in our discussion included the potential environmental impact of testing (the environmental impact of Rapid Flow Assays has been significant), the psychological impact of receiving a diagnosis, and the need to engender trust in the public, as a diagnostic test is useless if the recipient does not trust the result. One idea we’d like to highlight in particular:

Equity

Clare made the pertinent point that healthcare resources are extremely limited, and that those who need these tests the least also unfortunately have the most buying power. It is important that when deciding what potential applications to highlight, we do not advocate for over-testing or over-screening, and pick tests that will make a difference. Specifically, tests should not be created just “for the sake of knowing.” From a public health perspective, for something that is publicly funded, they should not be targeted at the mother who just wants to know what exact strain of cold their child has, despite the diagnosis not making any clinically relevant impact.

How We Responded

At this stage it is important to recognise that we as a team, developing our technology, are not able to fix the systemic issues discussed here. As a foundational advance team, we are not producing a particular ready-for-implementation solution, and there would be many more hands between ours and those who decide what gets made, and those who decide how things would be rolled out, not to mention the final end users. What we can do, and have done, is carefully consider which implementations we are choosing to highlight as potential applications that could impact the health sector in a positive way, according to what we have learned and researched.

Dr. Maureen O’Malley, Philosopher of Microbiology, University of Sydney

We met with Dr. Maureen O’Malley from the University of Sydney’s History and Philosophy of Science Department. Maureen is a philosopher of microbiology and the life sciences in general, a published author with over a decade of experience in the field, including work with synthetic biologists in particular. Our team benefitted from her critical eye and unique outlook.

Constructing a Narrative

Maureen was invaluable in assisting us in the refining of our project description. We presented an early draft of our project description to Maureen, from which she had some key feedback. She identified core strengths of our project that we had not emphasised enough, such as the foundational nature of what we are doing. We realised by focussing on the applications to try and give a visualisation for our audience, we had neglected to champion the strengths of being foundational - that it can be applied in a variety of ways, that it is a method that is core to what we are generating, rather than an end product.

Additionally, we were prompted to emphasise our equity and access considerations more. Maureen tempered some concerns that we had had that applications could drive an increase in expensive, cost-unefficient personalised medicine products, rather than increasing access for those in remote areas or with fewer funds. We were reminded that it would be a completely unreasonable expectation for our small project and resulting technology to fix the healthcare system and make it equitable; The only expectation of us is to do something that we can hope would be accessible to those who need it regardless of the inequities in the system.

How We Responded

We’ve responded to Maureen’s feedback in our project description page, homepage of the wiki. This can be compared back to earlier iterations of descriptions of our project, such as our project proposal or promotional video.

Healthcare Applications and Overpromising

“The way to sell a product in these days is to oversell.”

When the topic of our potential applications came up, we had a general discussion about the potential harms of healthcare startups overpromising the effects of their outputs. Maureen had a very balanced view on this. She emphasised the importance of being honest about what the obstacles with implementation would be, the problems faced at each stage of the project on the wiki, but also reminded us that you can be too anticipatory of the problems.

How We Responded

We were solidified in our view that we should not stop before we start because of further downstream effects.

Podcast with University of Washington iGEM Team

To see a transcript of the podcast, click here!

Together with the University of Washington team, who are generating melanoma take-home tests, we recorded a podcast discussing the implications of point of care and take-home testing in the Australian and United States contexts. Some key themes discussed included the differences in skin cancer prevention and treatment in the two countries, issues of equity and access, and the harms of overtesting.

To learn more about the collaboration, please go to our Collaborations page.

Surveys and Emails

Our team also created two surveys, one for rapid antigen testing/rapid flow assays and another for protein purification, targeted at the general public and biochemists respectively. Pdfs of the surveys can be downloaded here: survey 1 survey 2

Unfortunately our surveys did not receive enough responses to be informative for our work, however we would like to include them here as they are documentation and proof of our reflection on the wider impacts and stakeholders in our project throughout the course of iGEM.

Other initiatives that did not receive a response include an email we sent out to Innovation Scientific, the local Australian manufacturer of rapid antigen tests in our state. In this email we were hoping to have a sit down to discuss the potential of our technology from an industry perspective, and what issues they may be able to foresee with scale up.

Acknowledgement of Country

Our Project in Context

Dr. Clare Skinner, Emergency Physician Sydney

Features of a Useful Point of Care Serology-based Test

“There’s no point in diagnosing something for diagnoses sake, [it is] only useful if you can do targeted treatment.”

An Expanded Range of Applications

"First Nations First: If what you’re developing wouldn’t work well in Hermannsburg, Northern Territory, then it doesn’t work at all."

Potential Issues in Implementation

“Any health tool you create will be overused by the healthy, worried, well and underused by people who actually need it.”

Dr. Maureen O’Malley, Philosopher of Microbiology, University of Sydney

Constructing a Narrative

Healthcare Applications and Overpromising

“The way to sell a product in these days is to oversell.”

Podcast with University of Washington iGEM Team

Surveys and Emails