Team:NUS Singapore/Integrated Practices



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Human Practices

This page provides information on how our team plans to integrate both of our human practices finding, namely Survey and Business Plan, to make a sustainable positive impact in cancer diagnostics. For more details, please visit the respective subpages of our wiki.


Integrated Practices

Biopsies are usually conducted to determine the specific cancer type that a patient has. As this method is invasive, involving the removal of body tissue for examination of cancer cells, researchers are looking into non-invasive cancer diagnosis methods. A feasible non-invasive cancer diagnosis method is via the use of the RIOT System. Bacteria engineered with the RIOT System have the potential to diagnose various types of cancers, and possibly deliver therapeutics into the cancer cells. These bacteria are intended to be delivered into the human body by injection near the site of the cancer.

As injection into the patient’s body is required for cancer diagnosis and therapy, we had to take into account the public’s perception of bacterial-based disease diagnostic and therapeutic tools in the design of our project. High receptiveness to such tools would mean that there is a potential demand for the RIOT System, while low receptiveness would indicate a need for active public education and engagement, possibly through workshops held in schools or community centres.

As several bacterial species are well-known as disease causative agents, we hypothesised that the public might be skeptical about bacterial-based disease diagnostic and therapeutic tools. With the plan of developing such a tool for international use, we investigated the perceptions and receptiveness of all age groups to bacterial-based tools through a pilot survey in Singapore, Hong Kong and Australia (see Survey). This international survey was intended to shed light on receptiveness to bacterial-based tools and determine the levels of public education and engagement necessary. Survey participants turned out to be generally receptive to bacterial-based tools, as opposed to our initial hypothesis and worries.

As the results from our survey suggested that there is a potential demand for the RIOT System, we proceeded to write a Business Plan which examined the environmental, safety and sustainability aspects of our bacterial-based tool. These aspects, along with a study of the manufacturing and financial legislations, allowed us to determine ways to reduce the production cost of our tool while keeping production methods safe and sustainable.

Below, we elaborate on how the issues of Safety and Finances were tackled in our project based on our survey and business plan.


Safety

The safety concern we discovered after implementing the survey was taken very seriously by the team, and we decided that the issue had to be integrated and solved through the incorporation of the RIOT Sensor, which is a kill switch. Bacteria engineered with the RIOT Sensor can only survive in the presence of high lactate concentrations, as experimentally validated in Proof of Concept, Demonstration and Description. These results showed that bacteria engineered with the RIOT System can detect and respond to lactate, and are also sensitive to small changes in lactate concentrations. As a result, in the case of an accidental environmental release, the sensitivity of the kill switch to changes in lactate concentrations will ensure that the bacteria die rapidly in an external, low-lactate environment. Along with the fact that the strain of bacteria (E. coli Nissile) used is non-immunogenic, this will ensure minimum damage in the extreme case of contamination and contact with members of society (Hodson et al., 1981).

However, measures must still be in place to confront the accidental release of the bacteria into the environment. We propose that, in the case of an accidental release, we prioritise the safety concerns by establishing partnerships with the Public Utilities Board (PUB) and Ministry of Health (MOH) in Singapore. For example, water supplies can be checked for continual contamination in the swiftest possible manner with resources from the PUB. As there has not been a prior study carried out in Singapore with regards to such contamination events, it is imperative that we formulate a plan of action should such an incidence occur with our system.

We also tackled the issues with safety of diagnosis when designing the RIOT Responder. As cancer cells have an upregulated expression of CD44v6 cell surface receptors, these receptors act as a biomarker for cancer diagnosis. Hence, the anti-CD44v6 antibody conjugation engineered in the bacteria will cause them to bind only to cancer cells. If the bacteria do not reach a cancer tumor in time, they will be killed in the low-lactate environment by the kill switch (RIOT Sensor). These integrated measures together ensure that there will be no danger of propagation or unspecific binding to normal cells inside a patient’s body during diagnosis or therapy.


Finances

When we consider the financial aspect, a typical cancer diagnosis (blood tests, mammograms etc.) costs between S$50 and S$1000. If the RIOT System passes clinical trials and can act as an alternative method of cancer diagnosis, the business plan outlines how we may be able to price diagnostic tests at a much lower price of S$100 each, which is possible with the non-invasive and specific nature of the RIOT system. This will lead to a yearly income of approximately S$81,000 after using S$100,000 to invest in the following year of the company’s development. In a few words, the profitability and financial stability the company will potentially have stems from the basic design of the RIOT System - by having a strain of bacteria that uses spatial markers which specify its targeting to cancer cells - thus making the system a sustainable product that can survive in the market in the long-term.

By also tackling the marketing of the RIOT System with local Manufacturing and Human Resource legislations in the business plan, we aim to reduce the cost of production of such a tool and the safety-related stigma attached with a new, unknown medical procedure. By guarding the financial stability of implementing the RIOT System, we will be able to reach out to more cancer patients and, ultimately, ensure that no patient is refused a diagnosis due to financial strains. In addition, this method of diagnosis can be carried out without any specialized equipment and in impoverished areas.


References:


  • Hodson, M., Penketh, A. R. L., & Batten, J. C. (1981). Aerosol carbenicillin and gentamicin treatment of Pseudomonas aeruginosa infection in patients with cystic fibrosis. The Lancet, 318(8256), 1137-1139.

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