Overview

Synthetic biology techniques as CRISPR-Cas9 have gained huge public interest for human enhancement and are becoming more and more accessible to the general public. In this light, we identified the need to promote responsible use of synthetic biology. The discussion on human enhancement takes a most prominent place in sports with the doping affairs and unites with synthetic biology in the phenomenon of gene doping, for which an implemented detection system lacked. Therefore, we decided to develop an efficient, reliable and versatile detection method for gene doping based on a thorough value sensitive design.
In the initial stages we presented our idea at the Bioengineering Institute Kickoff and immediately caught the interest of Clive Brown, Chief Technology Officer at Oxford Nanopore Technologies. Skype calls with the company ensued and drove us to switch our idea from a nanopore blocking to a pulling method.
Subsequently, we visited the VVBN conference on advances in doping to gain more insight in the field. Here, we met Dr. Dimeo, Professor in Sports Policy, who prompted us to extend our model to anticipate athletes’ choices in gene doping administration.
This idea to anticipate on future athlete behaviour also led us to organise the Hackathon at the Cyber Security Week. By letting engineers hack our detection method, we obtained additional variations for possible gene doping sequences, which were automatically added to our database.
Then, we presented our project for life science experts at the Delft Health Initiative where we discussed the impact of gene doping on the environment and future generations. This led us to involve a broader public through the organisation of the first Dutch Biotechnology Day characterised by debates we instigated on trains throughout The Netherlands.
However, we wanted to take it further and organised an expert discussion on the topic at the University of Stirling, Scotland’s University for Sporting Excellence. Here, we focussed on the differences between gene doping and more conventional doping in all aspects and how scientists should respond. Here, it became even more apparent how vulnerable athletes are to doping use and our approach to education was reinforced to close the loop for future responsible research.

Approach

As a team we highly value responsible research. Therefore, we wanted to make sure our project is responsible from the start till the end and beyond. This we made sure by passing our project through the phases that constitute Responsible Research and Innovation according to Stilgoe et al. (2013), i.e. anticipation, inclusion, reflection, and responsiveness.
The dimension of anticipation focuses on researchers investigating what is known, what is possible and what is likely in the field. This includes scenario building, making an assessment of their plausibility through interaction with experts as well as the general public, and the stimulation of an open and multidisciplinary collaboration. This we did through surveys, train debates, and through visiting conferences to learn about developments in the field and to make connections.
Subsequently, inclusion targets the process of open innovation and user-centered design. It focuses on transparency and collectively challenging regulations and standards. Grove-White et al. (2000) argue that the public conversation should stretch further to include the debate on future social worlds, while critically rethinking the ‘social constitutions’ inherent to the technological choices – that is, the ethical, political and social implications of the development. This we did during inclusion processes as the train debates and the expert discussion in Stirling.
Throughout the project, the process of reflectivity is continuously going on. We, as scientists, are used to professional self-reflexivity during the complete product development process. Our team continuously challenged our detection and we even had an inter-team detection method hacking challenge. However, as was stated by Wynne et al. in 1993, responsibility makes reflexivity also into a public matter. According to Stilgoe et al. (2013) reflexivity demands scientists to publically combine their scientific and moral responsibilities. This has been a prominent focus from the choice of our topic till our final design as can be seen from our interaction with the many stakeholders involved and the design requirements we derived from that.
Lastly, we responded to all stakeholder input by making a value sensitive design by which we managed to answer all needs and preferences of our stakeholders to come to an optimal method.

1. Anticipation

As a first stage in Responsible Research and Innovation we focussed on addressing the need for gene doping detection as well as on making an assessment of the challenges constituting gene doping with respect to future worlds.

1.1 Relevance of Gene Doping Detection

Gene doping caught our team’s interest at an early stage. Having often been confronted with the application of gene technology to humans and animals, we got fascinated by the concept of gene doping, its challenges and opportunities as well as its social relevance. Due to a lack of an implemented detection method it is hard to assess whether gene doping is currently happening. This is then of course always the first question people ask us. How relevant is your research? We can say it is a more eminent threat than you might have expected.

Let us start with the timeline in figure 1. Here some of the most prominent events in gene doping development are sorted in time and as it appears gene doping might already be happening.

Figure 1. Timeline of gene doping use and development in society.

On top of the articles supporting the suspicion and availability of gene doping, we wanted to assess the topic further, which we did through train debates and public surveys complemented by athlete interviews and contact with the Dutch Doping Authority as well as sports organisations as NOC-NSF, the Dutch National Sports Organisation, and a sports psychologist. From our surveys it became apparent that in The Netherlands 16% of the general public would like to use gene doping for performance enhancement without necessarily ascertaining its safety, in China this is 55%. These high figures amongst the general public together with the enormous pressure that is put on athletes give an indication of the need for detection. As a sports coach in Stirling pointed out, given the huge amounts of money going on in doping development compared to detection, gene doping will already be happening for sure.

Figure 2. Statistics on the willingness of the general public to use gene doping for performance enhancement in The Netherlands and The People’s Republic of China based on 181 and 126 respondents respectively.

Given the huge amounts of money going on in doping development, gene doping will already be happening for sure!

Given the huge amounts of money going on in doping development, gene doping will already be happening for sure!
Sports Coach Stirling

1.2 Future Gene Doping Challenges

After we evaluated the relevance of gene doping detection, we focussed on the challenges of gene doping in the broadest context. We made a Stakeholder Map incorporating all stakeholders and their values. From this list that includes amongst others the doping authorities, athletes, sports clubs and coaches as well as physicians and fans, we identified our strengths and weaknesses. From there we grouped the challenges involved in gene doping in the following categories: health (both private and public, global and intergenerational), responsibility and social inequality. As it became apparent during the expert discussion in Stirling it are exactly these topics that make gene doping different from conventional types of doping.

These common values we addressed with the creation of our detection method and we discussed the topics in our expert discussion at the University of Stirling, where we talked about why gene doping detection is so important. Watch the movie on this discussion here.

2. Inclusions

In Anticipation we discovered the topic of gene doping in the broadest sense, both scientifically as well as ethically and socially. Subsequently, we took it further as a part of the inclusion process to involve as many people as possible for optimal design requirements for everyone. Here are some of the approaches we took in involving people from science, from sports as well as the general public.

2.1 Science

2.1.1 Hackaton

Figure 3. Advertising our Hackathon.

From our surveys we knew that 98% of the public feels strongly about maintaining strict doping controls. People feel that sports is only moderately fair and 75% is afraid of gene doping becoming a big problem in sports. Also, people generally feel they are not as up to date with developments in gene technology as they would like to be. These figures prompted us to involve the general public with a little programming experience in the fight against gene doping through the design of possible gene doping sequences.

On October 5th, 2018 we therefore organised a Hackathon at the Cyber Security Week in the Fokker Terminal in The Hague. The goal: engaging the public and especially computer scientists in developing their own gene doping sequences. We developed a software tool that learns from the ever growing database our participants helped create. This way, we improve gene doping detection together, so that we are able to detect new approaches in gene doping and to be one step ahead of the doping developers. We think that together we are stronger, inspiring each other. Many computer scientists joined our event and provided us with useful input from a different perspective.

Figure 4. The Hackathon at the Cyber Security Week in the Fokker Terminal in The Hague.

2.1.2 Stirling Expert Discussion on the Future of Gene Doping

We met professor Dimeo, Associate Professor in Sport from Stirling University, at the VVBN conference in Utrecht on May 17. After that inspiring meeting, we stayed in touch through a Skype call and email contact where we asked him questions on social aspects of doping as athlete privacy, behaviour, regulation and education. This resulted in mutual interest in each other’s research activities upon which we were invited to give a seminar on our project for experts in the field of doping and genetics at the University of Stirling on August 30th 2018. After this seminar we organised a discussion on how gene doping is different from currently more conventional types of doping and on how to best react to these differences, through regulation and/or education. This led to interesting discussions pointing at a general lack of education on gene doping and to the responsibility for germ line infections that cannot be transferred to second-generation athletes. The outcomes of the discussion are more elaborately described below in Outcomes and Implications. In the drop-down below the case studies we prepared for the discussion can be found.

Figure 5. Twitter comments on our seminar and expert discussion in Sterling, showing the impact and some new questions that arose.

Outcomes and Implications

The discussion took off very well, resulting in many opinions coming from different groups. The list of points that were identified to differ for gene doping compared to other kinds of doping is given in figure 5. The overall conclusion is that more attention should be paid to educating athletes on the risks above just regulating. Many athletes are not educated well about doping (and gene doping) and would therefore easily trust coaches etc. at the sports facility on their word to take in something of which they themselves are not able to oversee the consequences.

Figure 6. List of the differing factors between gene doping and more conventional doping.

Another topic adresses was that we cannot easily say that gene doping could become ‘safe’ at some point. Possibly it becomes apparent that we have been messing around with some feedback loops which has broader health implications on longer terms after some years. We cannot know with some initial studies. It is this what makes that we should be keep prohibiting gene doping according to the majority of experts present at the discussion. On top of this, differences in accessibility which you also already see in training facilities and equipment were used as arguments against gene doping.

Furthermore, it was brought up that there will always be differences between athletes, due to inherently different responses to gene therapies. Therefore, if everyone would be using gene doping, it is just like taking a step to somewhat higher performance, which will then level out again in time. So what would we achieve with doing it?

As became apparent in the discussion, the World Anti-Doping Agency (WADA) is not very open about gene doping to athletes and scientists. However, according to the experts at the conference, openness and involvement of the community could help a lot with the development of detection methods. This reinforces the community strength approach we take with for example the hackathon.