Team:Freiburg/HumanPractice/ethics

To deal with the ethical questions the application of our project could raise, we visited scientists of our university. After asking them for potential applications of the uniCAS toolkit we discussed the safety matters and ethical problems.
Many of these scientists saw a great potential in our toolkit to be an efficient approach for gaining new knowledge in their field of research. A few of them also mentioned the future perspective of using CRISPR/Cas for gene regulation in humans - for therapy purpose. This of course can be controversial discussed:

“… yet, there are already a lot of commonly used drugs that yield the same effects, even though more indirectly: via interactions with signaling processes that misconduct gene expression in certain cancer types ... ” (Prof. Dr. Wolfgang Driever, Developmental Biology)

A direct and therefore more efficient intervention of misguided signaling pathways could be achieved by introducing CRISPR/Cas to these cells encoded by RNA. Hence, the effect of this therapy approach would be only transiently. But, it is to consider, how the agents will be able to find the target cells and enter them, and what risks this still entails:

“… leukemia has already been treated with comparable approaches. After all, you always need to assess potential off-target activities, efficiencies and – most importantly – a drug vector for medical approaches ...” (Prof. Dr. Peter Stäheli, Virology)

So there will be risks, but does that mean that this kind of therapy has to be banned?

“… you always need to carefully balance the arguments for such an approach in gene therapy: stable integration of proteins like Cas9 into a patient’s cell implicates a certain risk of carcinogenic chromosomal aberrations. On the other hand, would you deny the promising chance of such a therapeutic device to someone who is – until then – suffering from a lethal disease?” (Prof. Dr. Peter Stäheli)

To assess which kind of therapy is ethically acceptable, there have to be made up subtypes and consider about the borders between them:

“… there are four categories of medical treatment, with increasing ethical dubiousness: number one doesn’t affect any genes at all, the second only transiently changes gene expression, number three renders the genome of somatic cells and in the fourth, the germ line itself is affected - which is, without any doubt, a no-go. However, the transient application of this tool in human cells, when introduced by vesicle-coated RNA, would only concern category two.“ (Prof. Dr. Wolfgang Driever)

The question, which of these categories should be allowed, has to be discussed in society. That is where the politicians come in, as they are the people who make the regulations, but:

“... can politicians really assess research projects from their non-scientific backgrounds?“ (Dr. Jochen Holzschuh, Neuronal Development)

Nevertheless, there is a need for researchers to enter into a dialogue with the public, because the consequences of their work will hit everybody and:

“... a scientist can never stay objective in regard to his own project. Moral judgements, thus, always need to be developed with non-involved experts ...“ (Dr. Jochen Holzschuh)

So, before there can take place a discussion, all participants must have got to know at least some basically facts. That was one reason why we visited politicians and went to the science fair.
But even when strict regulations are set a scientist has still the responsibility to think of the potential consequences his results could be used to, because:

“... the perspective of progress and benefits will guide scientists from all over the world to continue, so regulation by the law of one country is not sufficient if scientists in other countries are able to continue their work …” (Dr. Jochen Holzschuh)

And therefore researchers have to keep in mind that:

„... as a scientist who creates a certain knowledge, responsibility does not stop at the end of his or her own work - instead, the duty of observing the usage of this knowledge by other scientists arises ...“ (Dr. Jochen Holzschuh)

In contrary to application on human beings gene engineering of animals is already widely used in research - also in behavioral studies. It has been shown that the behavior of some animal can be influenced by genetical manipulation. If this progress will go on …

“… a maybe possible stable control of complex behavior will raise the question if we are allowed to steer animals …” (Dr. Georgios Pyrowolakis, Fly Development)

So there are many open questions to be dealt with. As always in ethics an answer is not easy and can not be found by objective scientific methods. So scientists will have to leave their familiar environment and go for discussion.

International ethical conference
"Engineering Life:
To the ethical and societal relevance of synthetic biology"

We, the iGEM-Team of Freiburg, participated in an international ethical seminar about synthetic biology at the Department of History and Ethics of Medicine of the University of Freiburg. We wanted to learn more about synthetic biology from a different point of view. From the perspectives of ethics, law, biosafety and biosecurity synthetic biology appeared in an interesting new light. Due to the lectures our understanding of the appearance of synthetic biology in the society, the hopes and fears, grew tremendously.
The seminar was the last session in a variety of meetings during 3 years of an interdisciplinary project work. All meetings were gathered in the project with the topic Engineering Life: An interdisciplinary approach to the ethics of Synthetic Biology. Here, scientists of different institutions investigated in the field of synthetic biology with the aim to clarify

1. if it is justified to speak about creating life,
2. how the reproach against science to "play God" could theologically be interpreted,
3. how risks and chances of this field of research shall be analyzed,
4. if the legal regulations were appropriate,
5. how a clear definition can be found whether a construct is natural or synthetic,
6. if there is a divergence in the systematical conditioning and actual research in synthetic biology.

On 26/9/13 it was discussed how a future society based on biotechnology could look like. Therefore, several movies from the Bio-Fiction film festival in Vienna were shown, where artists and filmmakers should visualize their associations with synthetic biology.
Here, the panel discussion came to the result that many of the movies showed the chances but also the risks of synthetic biology. Some aspects of mythology reappeared in the movies e.g. breathe life into a golem or opening Pandora's box.
In general, the risks always seemed to have a stronger effect on the audience than the benefits had. Furthermore, synthetic biology seemed to be connected with some kind of industrialization and a symbiosis of nature and technology. Regarding biosafety and biosecurity issues any genetic exchange between synthetic organisms and natural organisms should be prevented. Scientists support a clear separation of those, so that several approaches have been made. Here, xenobiological ideas e.g. alternative sugar-backbones [1] or chlorouracil [2] in the structure of D(X)NA are worthwhile to mention.

The next day, on 27/9/13, genetically engineered machines were in the focus of the curriculum. During the discussion catchwords such as "living machines" or "creating life" arose which led to the question if mankind was simply imitating God or if creation was no divine prerogative anymore.
With these questions in mind the discussion went into a direction, where the role and the character of human beings were exposed in the light of synthetic biology. It was realized that within synthetic biology homo faber, a human that changes and modifies his environment, evolved to homo creator, a human that recreates his environment anew. With well-known literature at the back of their minds [3] the participants came to the result that synthetic biologists were still normal members of our society and their engineered machines not comparable to God's creation.

Despite, this led automatically to the question if we would be in need of new laws and limits in order to safe the original environment and to beware the society of a next generation of bioweapons. This was also the main topic of the last day of the seminar on 28/9/13.
Here, the panel discussion showed that differences in e.g. european and US-law make it difficult to assure the safety of the environment. Therefore, it was suggested that a global gremium should adjust international laws concerning biotechnology and synthetic biology. This reminded us of the dual-use debates following a moratorium of several scientists who were working with so called superviruses in 2012. During this debate Global Health Security Policy Board additionaly to the NSABB was recommended by several scientists and scholars.

Hence, a debate about Do-it-yourself biology and so called biohackers was initiated. Thus, the defintions of biosafety and biosecurity were elaborated referring to Kelle:

"While biosafety measures aim to prevent the unintentional exposure to pathogens and toxins, or their accidental release, biosecurity measures focus on the prevention of theft, misuse, or intentional release of pathogens and toxins [4] ."

The participants of the seminar submitted that biohackers as amateur biologists wouldn't represent any prior hazard to biosecurity since the access to laboratory devices is still expensive and difficult and the know-how not assesable enough. Further, it was considered that biohackers would risk their own health while working in inappropriate locations as private appartments and with low-budget or self-made devices [compare to 5]. Thus, biohackers were categorized to biosafety affairs. However, bioweapons, bioterrorism and other criminal organizations came in the focus of the talks.

iGEM was also mentioned several times during the whole seminar. It was described as a competition for young scientists where they can make their first experiences with the synthesis of systems and tools that shall facilitate the daily lab routine of synthetic biologists [compare to 6]. As our team participated on this seminar, we took the chance and presented our project in a poster session. Philosophers, theologists, bioethicists and scientists were interested in our presentation and asked completely different questions to our project. Interestingly, most of them knew CRISPR/Cas and other systems for gene regulation. Their questions were e.g.

1. if we were able to regulate endogenous genes ,
2. if we had implemented our uniCas-toolkit into a stable cell line or into a model organism as mus musculus,
3. if we had any idea to increase biosafety or biosecurity concerning our project?

Here, we could indicate on our safety forms and explain our thoughts about risks and chances of a standardized uniCAS toolkit.

The seminar has clarified that synthetic biology as a young science causes lots of discussion and connects great hopes but still some fear in regard to biohackers and bioweapons. On one side the attitude of society to preserve the natural and on the other hand societal expectations to create something synthetic to protect the natural are forming a tension. This causes us to rethink. Thus, the mutual exchange expanded the horizons of the participants.

In the end of the seminar, we saw iGEM and our human practice efforts from a different angle. We were aware of the duty as synthetic biologists to demystify our science and laboratory work and to explain it to the society.

Speakers of the Engineering Life seminar:

Dr. Iñigo de Miguel Beriain, Bilbao / Dr. Jane Calvert, Edinburgh / Prof. Dr. Peter Dabrock, Erlangen / Dr. Bernd Giese, Bremen / Prof. Dr. Kristian Köchy, Kassel / Prof. Dr. Carlos María Romeo-Casabona, Bilbao / Prof. Dr. Jan C. Schmidt, Darmstadt / Dr. Markus Schmidt, Wien / Dr. Christoph Then, München

Participants of the Project:

PD Dr. Joachim Boldt, Freiburg / Matthias Braun, Erlangen / Christopher Coenen, Karlsruhe / Tobias Eichinger, Freiburg / Prof. Dr. Armin Grunwald, Karlsruhe / Reinhard Heil, Karlsruhe / Dr. Harald König, Karlsruhe / Prof. Dr. Giovanni Maio / Harald Matern, Erlangen / PD Dr. Oliver Müller, Freiburg / Dr. Rainer Paslack, Hannover / Dr. Jens Ried, Erlangen / Jürgen Robienski, Hannover / Prof. Dr. Jürgen Simon, Hannover / Prof. Dr. Hilmar Stolte, Hannover / Prof. Dr. Wilfried Weber, Freiburg / Hanna Wischhusen, Freiburg

References

(1) Schmidt M. 2010. Xenobiology: a new form of life as the ultimate biosafety tool . Bioessays

(2) Marlière,P., Patrouix,J., Döring,V., Herdewijn,P., Tricot,S., Cruveiller,S., Bouzon,M. and Mutzel,R. (2011) Chemical evolution of a bacterium's genome. Angew. Chem. Int. Ed., 50, 7109-7114

(3) Gibson et al. Creation of a bacterial cell controlled by a chemically synthesized genome., Science 2010 Jul

(4) http://www.idialog.eu/uploads/file/Synbiosafe-Biosecurity_awareness_in_Europe_Kelle.pdf

(5) Schmidt M. 2009. Do I understand what I can create? Biosafety issues in synthetic biology. Chapter 6 in: Schmidt M. Kelle A. Ganguli A, de Vriend H. (Eds.) 2009. Synthetic Biology. The Technoscience and its Societal Consequences. Springer Academic Publishing

(6) Schmidt M. 2013. Biosafety Considerations of Synthetic Biology in the International Genetically Engineered Machine (iGEM) Competition BioScience 25, Vol.