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Practical Guidelines for Ethics in iGEM - Part 2

The iGEM context Let’s return to the world of iGEM. We will now try to show how the method of casuistry can be applied to the work done in iGEM. The application of casuistry to your work will hopefully not only give you some clarity about the relevant moral landscape your project inhabits, but will also give some weight to the moral conclusion you make by making explicit the train of thought leading to them. We will illustrate casuistry in practice by taking two iGEM teams as case studies. The first will be ourselves, the team for University of Copenhagen (Denmark). The second case will be concerned with the team from University of Lund (Sweden).


iGEM Copenhagen - CIDosis This year’s iGEM team at the University of Copenhagen is focusing on helping people with chronic inflammatory diseases (CID).

We are producing a yeast-based biosensor that will be placed in a patch and will detect inflammation levels in sweat. We hope to replace invasive tests, and reduce the need for CID patients to visit hospitals.

The product is designed to make tailoring medication dosage and type to the patient easier, and to be used at home without direct supervision of a physician. Hopefully, this will make for more effective treatment of CID patients given that the ability to discover inflammation spikes quickly and react accordingly should be a great medical tool. We won’t get into the science behind the project since it is not relevant for the moral issue under review here. (If you are interested to explore more about it: https://2020.igem.org/Team:UCopenhagen)

A moral grey area that became apparent to us in the process of developing this project was the potential dangers of taking parts of patient care out of the direct control of physicians. Our product will not pose any physical danger to the patient (assuming it is used properly - which of course raises another ethical concern), but there is a possibility that the information provided by our product will cause some mental distress for the patient. It is conceivable that patients being more or less alone in interpreting the result of our home monitoring device will cause mental distress due to wrongful interpretation of results, or due to not knowing how to act on the results given.

When tests are administered on-site such problems are minimized. When test results are mediated to the patient through a healthcare professional it is less likely that the patient will walk away not knowing the seriousness of their condition. Furthermore, the healthcare professional can give immediate expert advice on how the patient should alter their behaviour based on the test results. Lastly, the healthcare professional is in a perfect position to mitigate and minimize the personal distress a patient might experience upon receiving bad news. Given these concerns, how do we evaluate whether a realization of our product would be morally permissible? First we set up a hypothetical case in the morphology step.


Morphology of a CIDosis case Debbie has Rheumatoid arthritis​. ​She has been given the option to self-monitor her inflammation levels by using a CIDosis patch. She wears the patch in the manner instructed by her physician, and notices that the results indicate a markable inflammation spike. Being worried about her own physical well-being, Debbie overestimates the seriousness of the results and gets anxious, depressed and a feeling of general distress​.

Are we at CIDosis responsible for the mental distress felt by Debbie? First what is the relevant morphology of the case? The mental distress felt by Debbie is certainly relevant. The seriousness of the mental distress should also feature. Furthermore, other important factors are whether she wore the patch voluntarily, whether the patch is important or otherwise beneficial for her treatment plan, whether she has received proper instruction and more. We have mapped out the facts of the case. However, as mentioned this is only the first part of the morphology step. The second part is formulating moral maxims that give identity to your case. Some of these count in favor of CIDosis. A plausible moral maxim is that one should respect the autonomy and the expressed wishes of the patient. However, a problematic moral maxim also applies. Namely, that one should not cause undue mental distress to already vulnerable people.

Taxonomy of a CIDosis case Given that we are seeking to resolve a moral ambiguity, we should base our taxonomic ordering around the problematic moral maxim in our case. First we should formulate an appropriate paradigm case that shares the same moral identity illustrated by our problematic moral maxim. The moral identity of our case is partly made up of the morality of inflicting mental distress on people. Our paradigm case should reflect that. We can take some instance of psychological torture as our paradigm case. Our paradigm case can be an instance of the psychological torture technique often called “mock execution”. We can use a historical instance as an example.

In 1849 the russian author Fyodor Dostoevsky, along with other members of the Petrashevsky circle, were arrested for high treason against the tsarist regime. Dostoevsky, along with 21 other members, were sentenced to death by firing squad. The group was taken to a remote location, tied to pillars and blindfolded as preparation for the execution. In reality, the Tsar had pardoned the group the day before, and had set up this theatrical show to engender terror in his subjects.


I think we can all agree that intending to inflict mental distress in this way is morally wrong, and unambiguously so (you can formulate your own example if you think the intuition is too weak). Our case will be far removed from this paradigm case, but we can now sort out the differences in morphology in order to see what factors carry moral weight. If we start out by assuming that the paradigm case exhibits a moral wrong-doing beyond discussion, and that the moral conclusions we can draw from our case is at best ambiguous, then we know that the difference in morphology carries some positive moral weight.

So what are the differences? Firstly, in the paradigm case the mental distress caused is most likely more severe than in our case. Secondly, in the paradigm case coercion is involved, while our case makes explicit that the patch is worn voluntarily. There are undoubtedly more relevant differences, but the last one I will mention is that in the paradigm case the mental distress is the intended consequence of the action, while in our case it is an unintended side effect.

Kinetics of a CIDosis case We are now in a position to draw some moral conclusions about our case. As mentioned before ​kinetics is where practical reasoning comes in and we need to rely on previous experience and our knowledge of the circumstances. However, given that the circumstances featured in our case makes it morally ambiguous compared to the paradigm case, we can be certain that these circumstances serve as a necessary condition for our case to be morally permissible. Our case might exhibit a moral wrong for reasons not discussed, but if it is to be considered permissible to inflict this kind of mental distress on Debbie, then the circumstances that make the case different from the paradigm case needs to be in place. How much one should weigh these differences is difficult to answer. For example, what is the acceptable amount of mental distress inflicted unto Debbie? This will depend on the other circumstances of the case, like how essential the patch is for her treatment plan, whether she has been instructed properly and consented to using it etc. There is no formula for weighing these things, but at least we now know the morally relevant factors. This means that any attempt to bring a project like CIDosis into the world needs to make sure that some conditions are in place. For example, we would need to make sure that patient autonomy is respected, that the mental distress inflicted is of a negligible nature, that explicit and informed consent is made by the patient, and so on. All of these conditions might be in place, and the CIDosis project might still be morally problematic for other reasons, but if one of the conditions is missing, we can be certain that the project has some problematic aspects. That is, after making our analysis we know that we should incorporate some framework that allows for informed patient consent, and so on.

iGEM Lund - Protecto The 2020 iGEM team from Lund focuses on helping out potato farmers. A big problem for farmers is potato crops getting late blight ( also called​ Phytophthora infestans )​. Late blight causes infection in potato tubers and causes problems with putrification of potato crops. There is no known cure for ongoing infections of late blight, and prevention emphasizes heavy use of pesticides. For example, in Sweden potatoes account for 2% of swedish crops, but 21% of pesticide usage is used on potato crops. Pesticides have been linked to premature deaths, chronic disease, as well as the destruction plant and animal habitats. Another issue with pesticide usage to prevent late blight, is that it develops resistance. This means that preventive treatment requires interchangeable alternatives in case resistance to one compound is developed. The impact of pesticide use is large, and the need for more efficient environmentally friendly and non-hazardous pesticides is clear.


Morphology of Protecto Protecto is working towards such a goal. Plants have been exposed to fungicides for millions of years, some have developed different ways of fighting them through certain antimicrobial peptides.

By combining different antimicrobial peptides and forming them into a cocktail, the end result would provide a more durable structure over time.

A two-plasmid system allows for use of a fusion partner without needing to add separate protease to cleave the fusion protein. This, in turn, allows for an efficient and sustainable system. Our main goal is to be able to release this product into the environment and help put an end to Phytophthora. Hence, an optically regulated (optogenetic) kill switch was incorporated to our project design to make the future of GMOs possible. Not only that, but our project also lays ground for the development of sustainable pesticide alternatives. This is the relevant facts of the Protecto case. (You can read more about Protecto here: https://2020.igem.org/Team:Lund)

An ethical issue facing Protecto, along with a lot of other iGEM teams, is the potential of releasing genetically modified organisms into places where they are not supposed to be. There is a danger that releasing GMOs into nature could lead them to proliferate and have unintended consequences. In some cases the danger is that genetic contamination occurs, or that the introduced GMO organisms have a competitive advantage over natural organisms, which might allow them to become invasive, spread into new habitats and cause ecological damage. Furthermore, there is a danger that we have no course of corrective action once GMOs have been released into nature. The danger of introducing a GMO organism into an environment might not be greater than the danger of introducing a non-GMO organism, but this fact does not exempt it from scrutiny. The moral maxims that applies to such GMO cases might be something like “action should be limited if there is sufficient uncertainty regarding what the consequences might be, and the risk of those consequences occuring” . That is, the most relevant moral maxim that applies to the case is one that emphasizes a precautionary approach to releasing GMO into nature.

Taxonomy We have mapped out the case, and identified a moral maxim that applies to it. We can now set up a paradigm case that shares the moral maxim. A non-scientific historical paradigm case can be found in the actions of the American ornithologist Eugen Schieffelin. Schieffelin was a member of the American Acclimatization Society, a society focusing on introducing new plant and animal species from one part to another. In the years 1890 and 1891 Schieffelin released 100 European Sterlings into New York city, because he believed the US should have all the birds mentioned in the plays of William Shakespeare (The European Starling being such a bird). Today the European Starling is considered an invasive species in the US due to their destruction of crops, and the fact that they carry with them parasites and diseases, making them a potential risk for livestock industries.


The consequences of Schieffelin’s actions were undoubtedly negative and unintended. Furthermore, The “precautionary approach” principle, which he clearly did not act in accordance with, applies to this case. Arguably, the case represents a clear wrong-doing not just because the consequences happened to be negative, but because Schieffelin failed to evaluate that such an action might have unintended negative consequences at all.

(3) One could also argue that a moral maxim that applies to GMO cases is “one should not disturb the integrity or intrinsic value of the organisms involved in GMO technologies”.

It is possible to make some comparison to the Protecto case. Firstly, the motivations behind the Protecto project are arguably more noble than the motivations of Schieffelin. Avoiding infected potato crops arguably offers a greater benefit than whatever the poetic goals Schieffelin wanted to achieve was. Furthermore, the alternatives to the Protecto product are already harmful for the environment, and it is reasonable to believe that Protecto offers a more environmentally friendly solution. Lastly, Protecto has taken active steps towards minimizing the possibility of negative unintended consequences occuring.

By incorporating a kill-switch into their project, Protecto has minimized the possibility that GMO could spill over into places they do not belong.

Kinetics in Protecto After being done with the taxonomy step, we can now move over to kinetics. As in the CIDosis case it is hard to evaluate how heavy one should weigh what differentiates the Protecto case from the Schieffelin case. However, we do know that the difference takes us from a case which is unarguably wrong, to a case where it is much more reasonable to assume that the case exhibits a morally righteous action. Taken together these differences in fact constitute necessary conditions that need to be in place for the Protecto project to be morally permissible.

A step by step summary This is intended to be a condensed step by step guide for how to proceed with casuistic reasoning about your project.


1. Mapping out your case One should always start with describing your case in detail. Your description should be so detailed that it becomes apparent where the moral ambiguities lie, and where your moral work should be focused.

2. Identifying relevant moral maxims After successfully mapping out your case, you should identify the relevant moral maxims that apply to it. These are short, rule-like sayings that give moral identity to your case (see Part 1 of this article). Moral maxims do not allow us to make any moral judgement relating to the case, but it makes clear what the potential moral problem is. There are often several moral maxims that apply to a case, which is usually why our moral intuitions about it are muddled or confused.

3. Formulating a paradigm case We should now formulate a paradigm case that exemplifies a clear moral judgment (see Part 1 of this article). This paradigm case should to some degree share a moral identity with the case you wish to investigate. That means that at least one of the moral maxims that applies to your case, should apply to the paradigm case.

4. Compare your case with the paradigm case The moral judgments one can draw from the paradigm case are, just like in the case you are investigating, drawn from the facts of the case. Using the paradigm as an analogous case, you can investigate what similarities it shares with your case, and what differentiates them. The paradigm case exemplifies a clear moral judgment, while your case does not. This means that the facts that differentiates the cases carry with them some moral force which makes the conclusions one can draw from the cases different.

5. Practical reasoning and weighing the facts

At this stage you should try to evaluate the importance of the facts that differentiates your case from the paradigm case. You have established that your case contains some facts that make the moral conclusions drawn from it different than the one in the paradigm case. You should now try to evaluate which of these facts are most important for making the moral conclusions different. There is no straightforward way to do this. It requires reliance on previous experience, contextual information and common sense.

6. Sketching out the necessary conditions for you case In this step you should try to make some concrete conclusions about your case. Most likely you cannot know with certainty that your case is morally permissible, because it is always possible that it is wrong for other reasons than the ones illustrated by the paradigm case. However, you can with certainty say that what differentiates your case from the paradigm needs to be in place if your case is to be morally permissible at all. As an example, If euthanasia is to be morally permissible then some mechanism that respect patient autonomy needs to be in place. This does not mean that euthanasia is permissible if that mechanism is in place, but it needs to be there if it is to be permissible at all.


About the Author


Sources Bleyer, B. (2020). ​Casuistry: On a Method of Ethical Judgement in Patient Care​. In HEC Forum. Springer Netherlands​.​ (pp. 212) Jonsen, A. R., & Toulmin, S. (1988). ​The abuse of casuistry: A history of moral reasoning​. Univ of California Press. Jonsen, A. R. (1991). ​Casuistry as methodology in clinical ethics. Theoretical medicine, 12(4) (pp. 297-298, 301) Strong, C. (1999). Critiques of casuistry and why they are mistaken​. Theoretical Medicine and Bioethics, 20(5). (pp. 398)


http://www.todayifoundout.com/index.php/2015/02/execution-fyodor-dostoevsky/

https://www.britannica.com/biography/Fyodor-Dostoyevsky

https://anotherbagmoretravel.wordpress.com/2011/10/10/eugene-schieffelin-william-shakespeare-and-starlings-in-the-usa/

https://www.lindahall.org/eugene-schieffelin/

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