Ethical Discussion about Gene therapy

Working towards the future application of OPTOPTOSIS in humans, poses the question on how to insert our gene products in human cells.

Currently, gene therapy is the most applicable method mainly being researched since the late 80’s because of its promising potential. Especially, the usage of gene therapy for treating and preventing hereditary monogenetic diseases is widely accepted. In comparison to that, viral gene therapy used to alter individual abilities and genetic aptitude is less common.

Somatic vs. Embryonic Gene Therapy

Somatic gene therapy is still more accepted by the public than embryonic gene therapy. Embryonic gene therapy aims at repairing, changing or adding nucleic acid sequences in germ cells. Therefore these changes are inherited while the changes made in somatic gene therapy only concern the treated individuals. In Europe embryonic gene therapy mainly encounters denial and is forbidden by the “Schweizerische Bundesverfassung in der Eidgenossenschaft” especially because of ethical proviso as one might be able to determine the next generations’ destiny ^[1]. Intervention in the cells of the germ line are also prohibited according to the Embryo Protection Law. ^[2]

Approvement of gene therapeutical medicaments

Due to the sensitivity of the topic, the procedure of establishing gene therapeutical medicaments during non-clinical studies and before the first clinical use are differing in comparison to normal medication admission procedure. For example, the phase where the medicament is tested on fit humans is skipped. Additionally, the number of clinical subjects is reduced. For detailed information please read here.

Once a gene therapeutical medicament has been approved for clinical use, somatic gene therapy is an accepted method to combat incurable diseases. The usage of somatic gene therapy is often advised to patients when they have no other option for cure. Especially, if the possibility for recovery is higher than the outbreak of possible side effects of the therapy. In order to ensure the patient’s objectivity and autonomous decision, physicians are to enlighten them in regard of safety issues, possible risks and the procedure itself ^[2].

Public opinion of gene therapy

Even though, gene therapy is being researched and used since the 90’s, the public opinion and awareness concerning the topic are less tangible and developed than genetic engineering for agricultural use. ^[3]

However, due to recent cases where gene therapy resulted in the outbreak of other diseases, the public position was negatively affected. Especially one case was emotionally discussed in Germany. Between 2006 and 2009 a paediatric doctor and his team decided to treat nine children with Wiskott-Aldrich-Syndrome using gene therapy. At first, the treated children showed improvement in health, but after two years their health deteriorated. The patients were diagnosed with leukaemia and up to date three died because of the treatment. The treating paediatrician was accused that his decision to use gene therapy instead of trying to find suitable stem cell donors at first, was mainly driven by recent results that have been achieved in ameliorating the patient’s condition using gene therapy. ^{[4] [5]}

Such setbacks are perceived highly emotional in society and thus gene therapy is recently being discussed quite arbitrarily. At the beginning of the research, cases like the one mentioned above often occurred and researchers decided to postpone premature publishing of experimental outcomes and rather focused on further researching the molecular biological essentials of gene therapy. The research is consistently continuing because of occurring risks and problems in the implementation process. Even though researchers made the effort to systematically establish gene therapy it is publically disregarded due to those kind of events. During the first moments of media publishing, the public is often agitated and has a negative stance toward gene therapy. Thorough investigations and discussions often contribute to balanced discussions.

To detect the current public point of view towards gene therapy in general and how the usage of gene therapy on oneself is perceived in the public eye, we conducted a survey.

Responsibility of physicians and researchers

Physicians and researchers hold responsibility towards patients and the public. On the one hand, they have to ensure the safety and well-being of the patients, on the other hand they have to test and establish new and promising therapies. Their judgement has to be constantly developed and further broadened through experimental clinical studies. Especially since gene therapy is being controversially discussed, physicians have to be careful and thoroughly prepare patients for the procedure. The following points have to be considered: Safety, patients’ autonomy, moment of implementation of the study, therapeutic alternatives, expected effects, unintentional and/ or unforeseeable sequelae.

One strongly shared opinion of public and experts is that the therapy has to be constantly improved and made safer before it can be considered as a regular therapy method. Expert’s prediction is that the more about pathological biology is revealed, the more established gene therapy may become. As mentioned before, due to negative incidents in the 90’s such as clinical setbacks and outbreaks of other diseases, the focus was especially put on the research and development of safer and more efficient vectors. The reason was that many vectors induced severe immune reactions and led to the outbreak of other diseases ^[3].

Known vectors are for example Retro-Virus, Adeno-Virus and Adeno-associated Virus (AAV). A very recent version of a vector was published by the manufacturer PlasmidFactory, so called Minicircle DNA, where the resistance genes were completely cut out from the genome to make the transfection process safer.

Acceptance of somatic gene therapy

In professional essays and statements of different ethical commissions, therapeutical somatic gene transfer is considered to be an extension of existing therapy methods, even considering it to be an analogy to transplantations during the early rise of research on the therapy. ^[6]

According to the evaluation of the “Benda-Kommission” in Germany in the 1980’s, gene transfer in somatic cells was not considered fundamentally different in comparison to an organ transplant when discussing both topics on an ethical basis. During experimental stage gene therapy raises similar questions as new operation methods, that had yet to be established. The “Benda-Kommission” is a working group on genome analysis and gene therapy with the goal to promote ethical discussion on a political level ^[7].

Since gene therapy is considered to be a medical treatment form using gene transfer medications (section 4, paragraph 9 of the German Medicines Act), the legal admissibility of clinical test is mainly based on an assessment of risks and benefits for the patients.

Accepting the significance of the ethical postulate and working under the general conception that scientific and medicinal acts have to be for the benefit of mankind results in the ethical legitimation of somatic gene therapy as a therapy form with the foremost goal to cure. ^[3]
Though the viewpoint on research development of gene therapy for curing non-treatable diseases was especially positive, experiments and results made in the 90’s have to be rated cautiously. Many results were achieved under illegal conditions and procedures of the research and treatment, so that the transmission of the achieved results should be handled with care.

Nowadays, the consideration for using gene therapy are subjectively rated by the treating doctor. Afterwards, ethic commissions as well as the Paul-Ehrlich-Institut (PEI) decide individually about the use of gene therapy. Procedural pads and ethical indications have been formulated by the Bundesärztekammer and the DFG and can be used as guidelines.

Despite the positive attitude of academics towards gene therapy, the German public is less convinced. Both adversaries and supporters ask for stricter regulations in gene therapy to ensure the safety aspects. ^[8]

Having said that, the German public is not extremely biased towards gene therapy unlike green biotechnology, so street movements are almost non-existent here in Germany. Maybe also because, gene therapy concerns a little number of affected people on an individual level and not the majority on a communal level.

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sources: ^[1] = http://www.bats.ch/bats/publikationen/2002-1_somatische/somatische_gentherapie.pdf [last access: 10/10/2016]
^[2] = Fuchs M (2006), Forschungsethische Aspekte der Gentherapie. Berlin, S. 185-207, urn:nbn:de:kobv:b4-opus-23673. In: Fehse, Boris / Domasch, Silke (Ed.): Gentherapie in Deutschland : eine interdisziplinäre Bestandsaufnahme (Forschungsberichte / Interdisziplinäre Arbeitsgruppen, Berlin-Brandenburgische Akademie der Wissenschaften ; 27). Berlin.
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^[3] =Hucho F., Müller-Röber B., Domasch S., Boysen M. (2008), Gene Therapy in Germany. An Interdisciplinary Survey- Supplement of the German Gene Technology Report-Summary. berlin-Brandenburg Academy of Science and Humanities (Ed.), p.1-31
Download [last access: 10/3/206]
^[4] = Spiegel online article wbr/chs (4/22/2016) http://www.spiegel.de/gesundheit/diagnose/gentherapie-leukaemiefaelle-bei-medizinischer-studie-a-1088753.html[last access: 10/4/2016]
^[5] = press release from DKFZ (3/13/2014). Stem cell therapy: Chances and Risks http://www.dkfz.de/de/presse/pressemitteilungen/2014/dkfz-pm-14-10c-Stammzell-Gentherapie-Chancen-und-Risiken.php [last access: 10/4/2016]
^[6] source: President’s Commission for the Study of Ethical Problems in Medicine and Behavioral Research in den USA 1982; Benda commission Germany]
^[7]= http://www.ethikrat.org/themen/gesellschaft-und-recht/ethikberatung?set_language=en [last access: 10/3/2016]
^[8] = DFG (2006,2007): Development of Gene Therapy. Statement of the Senate Commission concerning Fundamental Questions of Genetic Research, 5th announcement. Wiley-VCH Download [last access: 10/02/2016]