2121In the run up to the Nobel Prize for Chemistry, Reuters released its annual list of predictions of the winners. Not surprisingly, among the leading candidates for the prize were Jennifer Doudna and Emmannuelle Charpentier, for discovering the CRISPR-Cas9 gene editing system. Hailed as one of the greatest scientific breakthroughs of our time, CRISPR-Cas9 allows researchers to rapidly and accurately make changes in the genome of an organism. The discovery has opened up the possibility of understanding fundamental biology like never before while also promising the next generation of therapies achieved through correcting genetic mutations.
Genome editing however, is fraught with ethical controversies, because of concerns surrounding permanently altering the human genome in a way that can be passed on to future generations, bringing forth fears of eugenics and human enhancement for non-therapeutic reasons. Many of those fears came to a head earlier this year, when researchers in China reportedthat they had, for the first time edited the genomes of human embryos. Though they had only used non-viable embryos that were incapable of developing into a fetus and reported that the technique was not very efficient, the mere attempt to alter the human genome amidst the lack of any regulations or discussion of risks involved in the technology, raised alarm bells among scientists and ethicists worldwide.
Leading researchers around the country including Dr. Doudna had earlier called for a moratorium on gene editing in human embryos, including for research purposes. The publication of the Chinese researchers’ work added many more voices against human genome editing studies.
It was to no one’s surprise then, that a Washington Post article news quoted many concerning voices from the US when it was reported that UK researcher Kathy Niakan of the Francis Crick Institute had applied for a license to conduct research using genome editing in human embryos to the Human Fertilisation and Embryology Authority (HFEA). The HFEA oversees all fertility treatment and embryo research in the UK.
Marcy Darnovsky, the executive director of the Center for Genetics and Society and a vocal opponent of genome editing in human embryos told the Washington Post, “This proposal is a troubling and provocative move…A global public conversation about preventing such misuses is just getting underway, and this proposal could short-circuit those deliberations.”
The global conversation she referred to is the international summit to be held this December, convened by the National Academy of Sciences to discuss the scientific and regulatory aspects of gene editing.
But should we be really worried that the process has taken a step forward in the UK?
Shifting views on genome editing research
Genome editing offers far too many opportunities to advance biomedical science that it is going to be extremely difficult, if not impossible to ban its use around the world. Even the group of scientists who called for a moratorium realized this, asking only that researchers temporarily halt such research until a regulatory framework was discussed. In the months following the sweepingly negative reactions to the Chinese researchers’ experiments, expert opinions have been steadily moving towards a more nuanced approach to genome editing. In September, the Hinxton Group, an international consortium of scientists, ethicists and lawyers issued a statement supporting the use of gene editing in human embryos for basic research while clearly indicating that there is insufficient knowledge about the technology to consider clinical reproductive applications.
Several experts who provided comments about the statement to the Genetic Expert News Service agreed with its conclusions. Dana Carroll, a professor of biochemistry at the University of Utah said:
The statement from the Hinxton Group is very thorough and thoughtful, identifying the most important issues surrounding the use of genome editing for human germline modification. Although they don’t say so explicitly, they seem to recognize the inevitability of such applications, and they sensibly focus on the research necessary to ensure that this is done safely. At the same time, they recognize the moral and ethical concerns that must be addressed, and they recommend, as others have done, that full public discussion be devoted to these.
I would like to hear a fuller discussion of the conditions and circumstances in which human germline therapy would be clinically the best approach, including consideration of the rights of the edited individual, before encouraging research with intentionally generated human embryos. At the same time, I agree completely that, ultimately, only through such research will the parameters for germline applications be determined.
UK’s regulatory framework ‘robust and sufficient’
When it comes to regulating human embryo research, the United Kingdom is one of the most well prepared to evaluate an application for genome editing research in human embryos. In 1982 following the ethical concerns surrounding the birth of the world’s first baby conceived through in vitro fertilization, the UK government convened a committee to discuss the scientific, ethical and legal aspects of the issue which eventually led to the Human Fertilisation and Embryology Authority (HFEA), a regulatory body that oversees all aspects of fertility and human embryo research in the country. Since then the HFEA has been tasked with evaluating several controversial advances in biomedical research, including the mitochondrial donation procedure recently approved by the UK Parliament –where healthy mitochondria from a donor egg replace faulty ones to cure prevent mitochondrially inherited diseases.
In contrast no such authority exists in the US. While the FDA would regulate any therapeutic applications of genome editing, the most control that the government has is regulating the use of federal funds for such research. This lack of federal regulation was at the center of the debate surrounding the creation and use of human embryonic stem cells for research in the first decade of this millennium. In 2001, when President George W. Bush signed a bill barring federal funding for establishing and using new human embryonic stem cell lines which, individual states and private foundations continued to legally support such research. In 2002, for example the state of California allowed human embryonic stem cell research and in 2004 voted to establish a 10-year $3 billion fund to support such research including work with cloned human embryos.
Similarly, while the NIH has indicated that it will not fund research involving genome editing in human embryos, there is no legal barrier for any researcher to conduct these experiments using private funding.
In the UK however, all of these activities would have to be approved by the HFEA irrespective of the funding source. And the regulatory framework is sufficiently robust to evaluate applications similar to those submitted by Dr. Niakan and oversee research should licenses be granted, says James Lawford Davies, a partner at the law firm Hempson in London and a leading legal expert in stem cells and human embryo research:
The application process for obtaining a research licence from the HFEA is extremely thorough and requires applicants to satisfy a HFEA research licence committee that the proposed research fulfils a number of requirements, including that the research is necessary or desirable for one of a number of statutory purposes (e.g. increasing knowledge about serious disease, or developing treatments for serious disease), and that it is necessary to use human embryos for the research. Applicants must also provide evidence of ethics approval by a properly constituted research ethics committee. If a licence is granted, it is time-limited for a specific duration, and the research is subject to on-going reporting and monitoring requirements.
It is a thorough process which can take a considerable length of time, and the HFEA has extensive experience of handling complex and sensitive applications for research, including applications to create human-animal hybrid embryos for research, and the use of mitochondrial transfer techniques to avoid the transmission of mitochondrial disease.
Davies who is also a member of the Board of Directors at the non-profit Campaign for Science and Engineering and an honorary lecturer at University College London believes that changing the law specifically for genome editing research is neither likely nor necessary.
I do not foresee any change to the law in the UK. As above, the use of gene editing in treatment (as opposed to research) is not permitted, and it would require an amendment to the primary legislation (the 1990 Act) to change this position. Perhaps more notably, I do not believe it is necessary for the legislation to be amended, nor do I support a moratorium in circumstances where the regulatory framework we have in place is sufficiently robust to ensure that only legitimate and ethically approved research will be licensed.
Moving forward, responsibly
While Davies does not see a change in the law, it is quite likely that the HFEA will take into serious consideration the recommendations that come out of the December gene editing summit which has been convened by the National Academy of Sciences in conjunction with the Chinese Academy of Sciences and the UK Royal Society. The committee will discuss the risks and benefits of using gene editing in human embryos and how such activities might be regulated. The eventual consensus report will strongly influence and guide how most countries around the world will approach regulating this technology.
By all accounts, it appears that all the stakeholders are doing the right thing in proceeding with caution and taking the time to discuss implications before issuing a recommendation. Genome editing certainly has risks involved and the ethical concerns expressed by many are indeed warranted. And while at first blush the it may appear that Niakan’s step forward is hasty, it is worth pointing out that she has taken the most responsible route in filing an application with the appropriate authority. Moreover, this is only the first step in a long and arduous process. The HFEA is sure to take many months if not more than a year to make a decision. Far from being concerning, this should be seen as an indication that a process that was specifically established by one country to regulate the science around embryo research is working.
Arvind Suresh is a science media liaison at the Genetic Expert News Service. He is also a science communicator and a former laboratory biologist. Follow him @suresh_arvind.