Team:TU Dresden/Human Practices
Beaming BioBricks from Space...
While developing our project, we realized that we also had to include the transgender community as one of our main stakeholders to act in a responsible manner, since our proof-of-concept experiment involves testing for the SRY gene.
Scientists could use our test in several manners, from a clone checking tool when working in the lab to mutant or knock-out screening in animal models or GMO-plants.
Doctors would extremely benefit from a DNA-testing-kit, since it can be used as a preliminary, easy and fast disease test when examining the individual risk and disease history of each patient.
Seniors are more prone to be affected by diseases and are therefore the main beneficiaries of our DipGene project.
The transgender community started to be involved in our project when we decided to test for the SRY-gene as a proof-of-concept experiment of our DipGene tool.
A big project needs the advice of brilliant people!
Our main goal during the IHP was to get in contact with both kinds of people that you need to consider while developing an entire project. On the one hand, there are those who are experts in the field. These people can give you very helpful hints, and will also benefit from the project, like it is the case with doctors and scientists. On the other hand, there are those stakeholders that may be interested in testing our DNA-testing-kit, namely the older population and the transgender community. This is why we decided to ask the experts for advices and possible ways of improving the project to broaden its applicability, but also talk to the beneficiaries, explain them what our project consists of and learn from them how to adapt the project to make it useful and responsible for the world.
How the experts’ advices
changed our project
How Paul converted our diagnostics tool into a dipping tool
At the very beginning of our journey, while designing our project, one of the very first stakeholders that we got in contact with was Dr. Paul Szekely. He is the director of the museum of biological collections of the UTPL (Universidad Técnica Particular de Loja) in Ecuador and our team member Sebastian used to work with him for a long time. Our DipGene project, based on developing a DNA-testing-kit, needed a novel DNA extraction method to make the tool as cheap and simple as we had it in mind.
We were struggling to solve the question how it would be possible to only get a color-readout of the fusion protein that we designed when the DNA of interest was bound and avoid the signal if it did not bind. By a fluke, Dr. Szekely presented the solution to us, when Sebastian contacted him to learn more about different methods of DNA extraction which could be interesting for our project. Learn more about this story on our design page.
The new DNA extraction method that he told us about came from a paper of 2017 written by Zou et al. In this method, DNA was extracted from a raw cell lysate by being bound on a cellulose paper disk.
Read more about Paul:
his work is fascinating
How Jesus broaden our project’s idea and its applications
Our project idea was initially fully focussed on the development of the DipGene project for the detection of different antibiotic resistances in microbial cells. However, it was Dr. Jesús Garcia de la Borbolla Serres who broadened our idea significantly by proposing to target human cells instead. Jesús is a doctor specialized in digestive medicine working in the hospital of “Virgen de Valme” in Sevilla (Spain). We originally called him via Skype to talk about the increasing risk of multi-resistant bacteria in hospitals all over the world and to ask him if a tool to detect those resistances in microbes would be needed in modern medicine, but he immediately realized that our idea could reach much further than only that. During a very fruitful Skype discussion he recommended us to broaden our project’s idea and develop a tool for monogenic disease diagnostics.
In our next team meeting we decided all together to take this new direction and broaden the applicability of our project to not only target bacteria but also to human cells.
How Dunja changed our mind regarding target genes
Our first thoughts were then to use our diagnostics tool to test for cancer genes, such as the BRCA gene for the predisposition of breast cancer gene. Few weeks later, asking for advice regarding dCas9 and the design of its guideRNA we came across Dunja Knapp, a senior research scientist in the Center of Regenerative Therapies Dresden (CRTD).
She advised us to change our idea, since cancer is often caused by point mutations and the genetic basis of many types of cancer is still poorly understood.
A much better application, she said, would be to test for longer integrations into the human genome. HIV would be a good target, especially since this disease is common in countries where limited access to advanced technology makes testing difficult. However, not only the accessibility but also privacy that our testing-kit would offer makes it valuable.
Read more about Dunja in our Attributions!
How a big audience voted for buccal swab DNA extraction
In order to combine the advice of Jesus and Paul and target human cells with the new extraction method we needed to start developing it for DNA extraction from human cells. Therefore, we had to decide what kind of sample should be taken from human patients. A decision that should be made by those who would be using the test in the end. Hence, we decided to ask a big audience what type of DNA they would prefer to donate, either buccal swab, blood sample, hair or urine.
We carried out a survey during one of the presentations that we held during the “Cellular Machines” lecture of Prof. Stefan Diez. (See our outreach for more information)
Since 80 % of the audience voted for buccal swab, we continued working on the DNA extraction of those samples. This audience consisted mainly of students in life science related master programs. We wanted to ensure that also our main stakeholders, people of advance age, would agree to donate their DNA that way. Therefore we went to the local community center to present our project to the seniors and asked how they would preferably donate their DNA for a genetic test. They all agreed that buccal swab would be the best way of taking a sample. (See our public engagement page)
How Stuart established our proof-of-concept experiment
Once the framework of the project had taken shape - we would develop a tool to test for genetic disease from human cells, but also for genetic insertions in microbial cells – we had to decide which genes to test for as a proof of concept. This was the moment when we got in contact with Prof. Stuart Maudsley, who is a group leader of the receptor biology lab in the Department of Biomedical Research at the University of Antwerp (Belgium). Stuart is an expert in neurodegenerative diseases - the main focus of his lab is to study how G protein-coupled receptors are related to the molecular signaling of complex aging-related diseases. That is why our team member Paula, who did an internship in his lab, thought about getting in contact with him.
We told him about our project and were interested in getting to know which genes were a feasible possibility to test for. While discussing different options, he came up with the great idea of using the SRY-gene (coding for a transcription factor) as a proof of concept, since it allows for a simple positive / negative testing. But this was not the only reason why SRY was a good idea. As described later, it is known that SRY-positive and -negative people differ greatly in their metabolism [1], which is of enormous importance, especially when it comes to drug development. [2] Medical care is nowadays still very biased towards SRY positive people, although SRY negative people may react very differently to the same type of drug. That is why identifying people as SRY positive or negative can be extremely beneficial, especially decoupled of their gender, as it is commonly done in studies or publications.
Stuart is extremely involved in achieving unbiased medicine and drug development and has performed very deep studies to characterize the key differences in metabolism.
Check out some of his highlights regarding this topic :
Article 1 |
Article 2 |
Article 3 |
Article 4
Stuart’s help was extremely useful, not only for establishing our proof-of-concept experiment but also to broaden our project involving new stakeholders: the transgender community.
Find more about Stuart and his work!
How the iGEM headquarters made us aware of the controversial aspect of the SRY gene:
On the 31st of August we submitted our safety form to the iGEM headquarters as every other team. In this safety form we talked about our proof-of-concept experiment of testing for the SRY gene. We received their kind feedback telling us how careful we have to be when talking about the SRY gene and its common association to the “male” or “female” gender roles in society. We therefore added a clear disclaimer to our wiki, in which we strongly state that our method is not to be used for the purpose of discrimination. At the same time we will only refer to people as SRY-negative or SRY-postive, never implying any gender association. Nevertheless, we informed ourselves about this controversy and got extremely interested in the transgender community’s opinion regarding our approach. Keep reading for more details!
How we shaped our project to
satisfy our stakeholders
After having followed the experts advices and having designed our project according to their opinions, we wanted to reach out to our other main stakeholders: people of advanced age and the local transgender community. Many genetic diseases start showing their symptoms with increasing age. Therefore it will be especially interesting to test for the presence of a predisposition to certain diseases. The outbreak of a disease can often be slowed down or its symptoms can be alleviated if the information about the risk of the disease is known in advance.
On the one side, we reached out to the seniors living around the area of our institute to bring them closer to modern science - see our public engagement website for more details – on the other side, we took great care to design our project to be easily applicable and understandable for everyone, even without a scientific background. Due to our proof-of-concept experiment of testing for the SRY gene, the local transgender community became one of our main stakeholders. We wanted to ensure that our project is good and responsible for the world and decided to get in contact with a transgender community, since none of us has experience on identifying gender-discriminative situations.
How we included the transgender community in our IHP and followed their advice:
We got extremely interested in including the transgender community in our IHP for several reasons.
Importance of the SRY gene in science:
It is known that SRY-positive and –negative people metabolize medication in a very different manner. [1] This is a broadly discussed topic especially when it comes to drug development, since this sex difference can alter the person’s response to drugs. [2] An analysis of new drug applications (NDA) proved the women under-representation in the analysis of many drugs in 1980 and 1990 [3], which can lead to extreme consequences.
Therefore, although we do not want to make a distinction between genders, we will stay with this gene for proof-of-concept, because until today there is a huge bias in medicine for SRY-positive test subjects in studying symptoms and approving new drugs. This is an inherent risk for SRY-negative patients whose bodies respond differently to the same drug or show different symptoms for the same disease, which can lead to mis-diagnosis or lack of diagnosis.
Getting the transgender community’s opinion to our project:
After realizing that testing for the SRY gene could lead to controversies in the transgender community, and since we personally do not have any experience on identifying if such a fast-SRY-testing kit may be used in a discriminative manner, we decided to get in contact with the local transgender community and ask for their experiences and their opinion about our SRY proof-of-concept experiment.
The local community that we got in contact with was the “Homosexueller/ transidenter/ bisexueller Verein Gerede e.V. Beratungsstelle” Dresden. After explaining them what our project and proof-of-concept experiment consists of they got very interested in knowing more about this test. We invited them to one of our meetings to have an open discussion, learn from their experiences and adapt our project according to their opinions.
Vanessa and Valerian (the representative of this transgender community in Dresden) were extremely kind to take several hours of their time to discuss with us possible controversial aspects of societal and ethical values as well as possible negative implications of our SRY-test.
The main outcomes of this fruitful discussion were the following:
In our modern society and in many countries there is still a very high risk of discrimination against people because of their gender. Vanessa listed several countries with a strong gender bias in their law system, in which transgender people could be tested on the street or upon entering the country. In their daily life here in Germany they experience many situations of discrimination and therefore perceive the possibility of having such a test out on the market as dangerous.
We agreed that if the test would be available on the market, we would provide it just for targeting monogenic diseases and only include the SRY-gene upon specific request / regulation: the customer must ensure that the person to be tested is aware of the ethical implications that this test could have.
Reviewing our thoughts of using the SRY-gene as a proof-of-concept to get easy positive/negative controls showed how the society and even us still imply cis gender identification as normal. To make sure that we do not further enhance this way of thinking, we reconsidered our decision and together with them we decided that testing for the X-chromosome would be a much better positive control. Nevertheless, they ensured that they and some of their colleagues from the transgender community would be very interested in testing themselves for their SRY-gene.
One of the comments of Valerian was:
German version:
Valerian: “Ich denke es ist total interessant (vorallem für die FZM(Frau zu Mann)-transgender) dass mal was entwickelt wird womit der Test auf Y-Chromosomen leichter wird. Was ich weiß ist dass wenn es wirklich eine einfache Methode gibt, dass ich der erste sein werde, der da Schlange steht und das macht.“
Translation:
“I think it is incredibly interesting, especially for the FTM(female to male)-transgender community, to develop something that facilitates testing for the Y-chromosome. What I know for sure is, if there is an easy method to test for it, I will be the first in the queue to get tested.“
His support made us decide to continue testing for the SRY-gene, however in case it gets commercialized, it would only be available upon request and associated with strict regulations.
At the same time we got a very good advice to always refer to people as SRY-positive and negative and never as male or female and to additionally request everyone using this test to follow our example. This way no gender roles are implied by the test and we hope to raise awareness for everyone using the test.
Furthermore, we also discussed how to represent the transgender community in our wiki and agreed that no stereotypic display of transgender-role models should be chosen. They recommended us to also not use the transgender symbol that we planned to include in our wiki based on the research that we did, but instead use the transgender flag. That is why our way of graphically representing their community has been with this flag throughout the wiki.
How we integrated the seniors’ opinion into our project:
One of our main stakeholders in our IHP and the main focus of our public engagement throughout our iGEM journey has been the older population. First of all, in order to ensure a responsible and non-offensive way of referring to them we did some research and decided to stay with the following article, claiming that the most appropriate ways are: older population and seniors. [4] That is why we will refer to them in one of the aforementioned manner.
It has become a fact that the population over age 65 has increased in the last 10 years and will keep rising for at least 20 years more due to the improved life conditions as well as the post-world war II baby boom. [5] The World Health Organization stated that the world’s population over 60 is expected to be a total of 2 billion in 2050, compared to the 900 million in 2015. [6]
Unluckily, aging is closely related to the development of different types of diseases as well as impairments. [7] Therefore, this population is the one benefiting most from our DipGene project and that is why we decided to include them as one of our main stakeholders: reaching out to them showed us how much interest there is to understand modern science and how little opportunities are offered to this specific peer group. This made us choose seniors as the main focus of our public engagement.
Performing several different activities with them has allowed us to understand that most of them are extremely interested in following our advances, but the way social networks are built nowadays does not help them. A lot of effort is put on bringing science closer to the kids, as for example events as “Science goes to school” or “the Long Night of Science” that mostly include activities thought for them. However, there has been a lack of effort on bringing science to the older population in a manner that they feel attracted by it and are encouraged to learn more. We wanted to change this and did our best and organized several activities to come closer to them.
First of all, we wanted to make sure that a genetic testing kit in the way that we were designing it would be wanted and people would be interested to test themselves. Therefore, we went to the community center for seniors “Begegnungszentrum Johannstadt”, presented our project and were overwhelmed by the approval of our project and the interest in modern science. While some people wanted to get tested directly and were sad to learn that we were still in the development phase of this kit, others were unsure if they wanted to have this information and we got into a very interesting discussion. It started with the comment of Hedwig asking how much information we could infer from her if she would donate her DNA.
Everyone agreed that the information about predisposition to diseases was very personal and should never get into the hands of anyone except for the person that the DNA belonged to. Direct-to-customer companies offering whole genome sequencing and testing for genetic diseases have been found to store and use customers data without their knowledge (for more information read our motivation page). The seniors with which we had the discussion had all the same very strong opinion about this issue: No company and especially no government should ever hold this potentially compromising information about their customers/citizens in their hands.
German version:
Britta G.:
“Wer hätte den dem Dritten Reich entkommen können, wenn die Nazis solche Informationen über die Bürger gehabt hätten? Man kann ja Pässe fälschen, aber nicht seine DNA.”
Translation:
“Who could have fled from the Third Reich if the Nazis would have held those informations about their citizens? You can fake your passport to flee, but no one can fake their DNA.”
Their opinion left a strong impression on us and we decided to include a part on the abuse of genomic information in our wiki to raise awareness of this problem and additionally to include a “DNase-spray” in the final kit which could be used to destroy all samples taken and all DNA extracted, so that everyone using the kit can be sure that the obtained information or samples could never get into hands they were not meant for.
References
[1] Institute of Medicine (US) Forum on Neuroscience and Nervous System Disorders. Sex Differences and Implications for Translational Neuroscience Research: Workshop Summary. Washington (DC): National Academies Press (US); 2011. 5, Sex Differences in Drug Development: Policy and Practice.
[2] Labots, G., Jones, A., de Visser, S. J., Rissmann, R., & Burggraaf, J. (2018). Gender differences in clinical registration trials: is there a real problem? British journal of clinical pharmacology, 84(4), 700–707.
[3] http://www.genderportal.eu/resources/fda-needs-ensure-more-study-gender-differences-prescription-drug-testing Date of Access: 12.10.2019
[4] Falconer, M., & O'Neill, D. (2007). Out with “the old,” elderly, and aged. BMJ: British Medical Journal, 334(7588), 316.
[5] Jaul, E., & Barron, J. (2017). Age-Related Diseases and Clinical and Public Health Implications for the 85 Years Old and Over Population. Frontiers in public health, 5, 335.
[6] WHO: https://www.who.int/news-room/fact-sheets/detail/ageing-and-health, Date of access: 13.10.2019
[7] Franceschi, C., Garagnani, P., Morsiani, C., Conte, M., Santoro, A., Grignolio, A., Monti, D., Capri, M., Salvioli, S. (2018). The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates. Frontiers in medicine, 5, 61
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