The birth of Lulu and Nana: testing the boundaries of freedom of research?
Dr Rumiana Yotova | rvy21@cam.ac.ukI. Genome Editing and the Case of Lulu and Nana
In November 2018, the Chinese scientist Dr He Jiankui reported the birth of the first genetically edited babies – Lulu and Nana- as a result of his editing and implanting of the embryos of seven couples with HIV-positive fathers in order to make them resistant to the virus. This announcement was met with universal condemnation and serious concern by scientists and International Organisations, strongly indicating that clinical research involving genome editing is not deemed to be acceptable at this stage. The Statement of the Second International Summit on Human Genome Editing, where the experiment was first announced held that ‘the procedure was irresponsible and failed to conform to international norms’ due to, inter alia, the ‘failure to meet ethical standards for protecting the welfare of research subjects and a lack of transparency in the development, review and conduct of the clinical procedures.’ The Summit ultimately concluded that ‘the scientific understanding and technical requirements for clinical practice remain too uncertain and the risks too great to permit clinical trials of germline editing at this time.’ Similar concerns were expressed in the statements in response by the Chinese Academy of Medical Sciences, the French National Academy of Medicine and the Academy of Sciences and the Nuffield Council on Bioethics. China’s Science Ministry reportedly suspended the scientific activities of those involved in the experiment, the Medical Ethics Committee of Shenzhen province opened an investigation into it and He was put under house arrest. In response, the WHO established a panel of experts to look into the international standards that should apply when editing the human genome with specific focus on interfering with the germline, i.e., the cells that we pass to future generations.
The genome editing used by Dr He in his experiment is a new, cheaper and more precise technique for genetic interventions that was developed in 2012 by Charpantier and Doudna. It is based on the mechanism utilised by bacteria to defend themselves against viruses using molecular scissors to cut unwanted sections of the DNA, insert desired ones or make edits. Genome editing can be performed on somatic cells, i.e., those that make up the body, or on germline cells, which are the ones we pass on to future generations. The latter type could arguably be more effective as it could be used on embryos with fewer cells; however, is also much more controversial given the scientific uncertainties in the use of this new technology and the unknown consequences that would be passed on to future generations.
In 2015, Chinese scientists reported using genome editing for the first time on non-viable human embryos to edit out a blood disorder with less than 20 % success rate. Despite these significant uncertainties underlying the use of the new technology, Dr He Jiankui edited the embryos of 9 couples with HIV-positive fathers even though the embryos did not carry the virus. According to observers, the unpublished data from the experiment indicates the presence of significant side effects in the form of off-target mutations and mosaicism in the twin babies. A recent scientific study further indicated that the genetic mutation that was the object of the experiment increases the likelihood of all-cause early mortality by 20 %.
Dr He’s experiment raises important questions regarding the extent and limits of the freedom of scientific research under international law.
II. Freedom of Research under International Law
Freedom of scientific research is a universally accepted and protected human right. It is set out in Article 15(3) of the ICESCR, in Article 15 of the Oviedo Convention, which provides for the freedom of scientific research specifically in the fields of biology and medicine, subject to the protection of human rights, as well as in Article 13 of the EU Charter of Fundamental Rights. The freedom of scientific research is affirmed in numerous soft law instruments, including Article 12(b) of the UNESCO Declaration on the Human Genome and in Article 2(b) of the Universal Declaration on Bioethics and Human Rights. Despite its nearly universal affirmation, however, freedom of research is not absolute. The preparatory works of the ICESCR reveal that the wording of Article 15 (3) whereby States agree “to respect the freedom indispensablefor scientific research” was qualified on purpose in order to preserve the regulatory space of States to limit the freedom when it goes contrary to public order, health or morality.
Soft law instruments in the field of human rights and genetics flesh out further the boundaries of the freedom of research. One boundary found across the legal instruments in the field is that limiting the purposes of genetic interventions to therapy, diagnostics and prevention. For example, the UNESCO Universal Declaration on the Human Genome and Human Rights specifies that “[t]he applications of research, including applications in biology, genetics and medicine, concerning the human genome, shall seek to offer relief from suffering and improve the health of individuals and humankind as a whole”. Similar provisions can be found in the UNESCO Declaration on Bioethics and Human Rights and the Oviedo Convention on Human Rights and Biomedicine. The EU Charter of Fundamental Rights expressly prohibits eugenic practices, indicating in the Commentary that ‘eugenics’ should be understood broadly and applied equally to State and non-State actors. According to the Commentary, this principle ‘constitutes a specific limitation on the freedom of scientific research’.
Another common limitation on the freedom of research is that it ought to be done with full respect for the human dignity, human rights and fundamental freedoms of the affected individuals.According to the Universal Declaration on the Human Genome and Human Rights:
No research or research applications concerning the human genome, in particular in the fields of biology, genetics and medicine, should prevail over respect for the human rights, fundamental freedoms and human dignity of individuals or, where applicable, of groups of people.
Indeed, according to the Committee on Economic, Social and Cultural Rights, States parties to the ICESCR are required to regulate to prevent the negative effects of science and scientific research. Related to this is the requirement of maximizing the benefits for the affected individuals and minimising of any possible harm through the assessment and adequate management of the risk related to medicine, life sciences and associated technologies.
III. Freedom of Research and Human Germline Editing: A Critical Appraisal
The implications of the freedom of scientific research for genome editing are that genome editing research ought to be allowed and protected so long as it is done for therapeutic, diagnostic and preventive purposes in a manner respectful of human rights and in accordance with the interests of the affected individual, as well as society. It is doubtful whether Dr He’s experiment was within the limits of the freedom of research as defined and protected under international law. First, it is not evident that the editing of the embryos in order to make them resistant to a virus that they did not carry was therapeutic or preventive, let alone to their benefit. This is due not only to the significant scientific uncertainties involved in using genome editing on human embryos but also to the unintended negative consequences caused by the mutation. Furthermore, Lulu and Nana were not affected by HIV and they could have been prevented from getting infected through much less invasive means. Second, there is no evidence that adequate measures were taken to minimise harm to the edited embryos, i.e. by way of impact assessment prior to an experiment which constituted the first ever use of genome editing in live human embryos. Third, it is also unclear whether the experiment was respectful of the human rights of Lulu and Nana, including their right to life, to health and to benefit from science. Finally, in the absence of binding regulation of genome editing in China or indeed on the international plane, it is far from certain whether any clinical research at this stage of scientific development is indeed in the interest of the public or of humanity as a whole.
Dr Rumiana Yotova is a Fellow and Lecturer in Law at Gonville and Caius College, University of Cambridge. She is also an Affiliated Lecturer at the Law Faculty of the University of Cambridge and an Academic Door Tenant at Thomas More Chambers in London.
