Market Analysis

The iGEM project started with a brainstorm session to decide in which direction we wanted our project to go. But before starting with our project, we had some crucial questions that needed to be answered. What tools are accessible today and what are their limits? Is there a market for a new diagnostic tool with our approach? Is there a need for a new diagnostic tool for large strongyles as well? How do the potential stakeholder or customer feel about using a diagnostic tool based on GMO?

To answer these questions we chose to proceed by setting up a meeting with the company Vidilab (a Swedish company working with diagnostics of parasites such as strongyles). Vidilab are everyday users of the current diagnostic tools thus are deeply involved and experienced within the area of our project, making them great consultants.

In addition, we conducted a survey to receive greater understanding of the individual perspective of the respondents. The survey was translated into 10 different languages, see table 1 .

Table 1. The table show the translational versions of the survey, sent in the market analysis, with highest amount of answers.

Ethics

The purpose of our project was to combat the systematic overuse of anthelmintics [1] (Salgado et al. 2016) and thus also address the growing resistance against such compounds. Resistance may arise from multiple factors, like that of mass treatment, underdosing and not varying the drugs used [2] (Shalaby 2013) which is not unlike how resistance against antibiotics arise [3] (Grenni et al. 2018). The resistance against anthelmintics might also be a problem for humans in the future [4] (Vercruysse et al. 2011) which increases motivation for a new diagnosis and-/or treatment approach. This is “good” news since the organism used in our project, namely the E.coli are inherent to the microbiome of humans and horses alike. We believe that a new, specific and potentially eco-friendly method of diagnosis or treatment would have a positive outcome on society as a whole. Lowering the degree of stress and potential suffering for animals that get infected as well as for their human owners.

There’s however some concerns in public about E.coli as being pathogenic or a transmitter of disease. It’s often the incidence when E.coli contaminated meat for consumption gets coverage in e.g. news media. It’s thus a challenge when conveying a complex topic to the public which demands some scientific knowledge, especially in biology and is something our Human Practise group has been challenged with throughout the project. The risks using E.coli and its given traits for this project are discussed further throughout the text.

The need for a new method, welcomed by the public

By authoring and distributing a survey to horse owners we could see that the majority of respondents in Sweden had positive attitudes (83.2 %, 368 respondents) towards a GMO-type of diagnosis method. The survey also showed a public fear of growing anthelmintics resistance against blood worms (77.3% of 370 respondents ranked their fear as 4 or 5 were 5 being the most concerned).

Environmental impact and risk

As new biomolecular technologies are presented, having a higher degree of specific interaction against targets and thus a lower ecological impact they may shift public opinion on synthetic biology and allow for other solutions to surface. This would possibly also bring interest back to the natural sciences and thus probably increase solutions that stem from e.g. synthetic biology.

As with most techniques or processes used, whether there be some exercise regimen for increasing athletic performance or treating crops with pesticides to ensure a certain yield, they most often have some sort of risk factor associated with them. No exception is made when organisms are taken from the environment undergoing genetically engineering which may modulate or even add capabilities. Risks associated with engineered organisms may be proliferation in the environment, organism being pathogenic, spreading of capabilities such as antibiotic resistance, synthesis of molecules that might be toxic or harmful to name a few. However, most nations have guidelines and laws regulating which entities operating in their domain must adhere to, whether they are companies, universities or individuals. As for members of the european union there are also an overlaying legislation which its members must follow [5] [6] (EFSA 2018, Papademetriou 2014).

The E.coli (BL-21, DH5-alpha) that was used in the lab has a biosafety level of 1, which is the lowest possible on a scale of 4 [7] (Stanford university 2018). That means e.g. that E.coli requires a minimum of safety precautions other than those provided by Uppsala university [8](GMO, bmc.uu.se).

Nothing that is considered toxic or harmful was genetically introduced (UnaG, amilGFP) for expression in our E.coli. However, for cultivation and selection purposes used in common synthetic biology practical work, antibiotic resistance was also introduced, which presents a risk in the potential spread of antibiotic resistance (Chloramphenicol, Ampicillin, Tetracycline) if these mechanisms were to spread into the environment. This was avoided to a large degree by following standard lab protocol with specific guidelines regarding waste disposal of GMOs as well as toxic chemicals, antibiotics and their likes.

The ability for proliferation of GMOs and organisms in general is determined by their fitness. As a rule of thumb regarding spread of GMOs in the environment, fitness is greatly reduced for most lab strains of microorganisms (model organisms) because they have been modified in numerous ways to make them easy to work with. This is not an adaptation that is suitable for their natural environment from which they originated. Add to this the metabolically expensive process in expressing proteins (UnaG, amilGFP) which can only be deemed as a negative fitness contribution [9] (Qiu 2013). Regarding risks associated with nematodes see separate safety document (https://2018.igem.org/Safety/Final_Safety_Form).

Noting that this was the first time one sought to see if this is a applicable solution to treat parasitic infections caused by nematodes in ungulates, it thus is a long way from a potentially finalized product. If in the future a product would surface, further risk assessments must be evaluated to see if an engineered product would be deemed safe to be orally ingested by a living host. Since enterio-diagnosis-systems based on bacteria is a novel approach there is little to be found in the litterature about its applied effects. However, this sort of assessment is out of the scope of our project and could not be, as well as, was never intended to be experimentally verifiable and only mention to give context and reasoning to future research if implementation of such product is to be realized. In addition to internal reviews, it is common for an external part (like governments) to perform reviews on the product, especially if the product is GMO classified. This is necessary to ensure that the product is safe before letting it hit the market.

Technologies can be used for good and bad. This well reversed statement implies that it’s not the technology itself that is either good or bad, rather its the use and implementation of technology that determines its consequences. Implying that its the use and the intentions of the user that sets the outcome, the user (including companies) should thus be held accountable for any unethical use. Bearing this in mind, that the operators behind a technology must be held responsible for his or her actions, saying no to upcoming technologies or research (such as those of enterio-diagnostic systems) would imply that people are not able to make the right decisions, with the emphasis on a hypothetical misconduct by a few. If this was the case we would have stopped before tied sharpened pieces of rock to a wooden shaft. We should instead treat people as responsible human beings and the development of a new technology as a bridge between an initial state and potential end state, whatever that end state might represent.

Disrupting commerce

Just as we’ve seen unprecedented advancements in technology in the recent years or in the last century there is no reason to think the future holds a different promise. Research is done both by academia and in the private sector. Their approach and funding often differs in the sense that a company have to make a profit from a product in order to be able to reinvest and stay competitive whilst academia are more self-sustainable in the means of grants and-/or other tax funded solutions as well as donations from various contributors. It might be that a new product developed through iGEM would put a business in a disadvantage, this is of course possible, but we feel this shouldn’t interfere with or discourage teams in their pursuit of new innovative solutions.

References

[1] Salgado JA, Santos C de P, Salgado JA, Santos C de P. 2016. Overview of anthelmintic resistance of gastrointestinal nematodes of small ruminants in Brazil. Revista Brasileira de Parasitologia Veterinária 25: 3–17.

[2] Shalaby HA. 2013. Anthelmintics Resistance; How to Overcome it? Iranian Journal of Parasitology 8: 18–32.

[3] Grenni P, Ancona V, Barra Caracciolo A. 2018. Ecological effects of antibiotics on natural ecosystems: A review. Microchemical Journal 136: 25–39.

[4] Vercruysse J, Albonico M, Behnke JM, Kotze AC, Prichard RK, McCarthy JS, Montresor A, Levecke B. 2011. Is anthelmintic resistance a concern for the control of human soil-transmitted helminths? International Journal for Parasitology: Drugs and Drug Resistance 1: 14–27.

[5] Genetically Modified Organisms. WWW-document: https://www.efsa.europa.eu/en/topics/topic/genetically-modified-organisms. Retrieved 2018-10-04.

[6] Papademetriou T. 2014. Restrictions on Genetically Modified Organisms: European Union | Law Library of Congress. http://www.loc.gov/law/help/restrictions-on-gmos/eu.php. Retrieved 2018-10-04.

[7] University © Stanford, Stanford, Complaints C 94305 C. Biosafety Levels for Biological Agents – Stanford Environmental Health & Safety. WWW-document: https://ehs.stanford.edu/reference/biosafety-levels-biological-agents. Retrieved 2018-10-04.

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[9] Qiu J. 2013. Genetically modified crops pass benefits to weeds: herbicide resistance and other genetic modifications could confer an advantage on plants in the wild. Nature 500: 389–390.