CRISPR technology now places the power to easily rewrite the genetic code of living organisms – including humans – into the hands of scientists worldwide. What type of oversight is required for this technology to deliver on its immense potential to improve the human condition? Scientific, regulatory, and governmental agencies are starting to get involved at the national level, but discussions and guidelines must extend beyond national boundaries, to support transnational policy diffusion and strengthen cooperation on a global scale.
Progress in international collaboration has largely been driven by global catastrophes and new technological developments. Wars, epidemics, and natural disasters reveal a shared vulnerability, while technological innovations, particularly in the fields of healthcare, transportation, and communication, increase our capacity to interact and bring us closer together. Efforts to aggressively pursue those innovations that unlock great areas of human potential must also be balanced, however, by parallel efforts that anticipate their potential disruptive effects on society, particularly when those effects cross national boundaries. This is especially so with a transformative technology that promises to redefine our relationship to the very building blocks of life.
Not long ago, basic research to determine how bacteria fight off viral infection seemed about as likely to impact human health as the sign of one’s horoscope. Since then, however, so-called CRISPR systems have transformed biomedical science by enabling researchers to make precise changes to the DNA of virtually any cell or organism. Proof-of-concept experiments in cultured human cells using this transformative gene-editing technology have erased the mutations that cause cystic fibrosis, Duchenne muscular dystrophy, and countless other genetic disorders. Research efforts already underway are applying these methods to develop new therapies that may alleviate or even cure genetic disease and certain cancers.
Yet the diverse applications of CRISPR technology, which go well beyond human therapeutics, are not without far-reaching ethical, legal, and social ramifications. Agricultural companies are harnessing new breeding technologies involving CRISPR to improve traits in plants and animals without the scars of gene splicing, blurring the lines of what is considered a genetically modified organism. In vectors of disease like the common mosquito, CRISPR-based gene drive technology is being developed to spread pathogen resistance into wild populations, an approach that could save thousands of lives but also irreversibly alter the genetics of native ecosystems in unknown ways. Perhaps most profoundly, the union of CRISPR and assisted reproductive technology may allow physicians to correct disease-associated mutations in human embryos such that changes would be inherited by all future generations, an application that has provoked concerns over equal access, a slippery slope towards genetic enhancements, and eugenics abuses.
While scientific research on CRISPR technology continues unabated, it is crucial that we step back to systematically investigate all the pros and cons, and to determine how proper governance can ensure that the products of research and innovation impact society in a beneficial manner. By placing the power to easily rewrite genetic code into the hands of scientists worldwide, CRISPR offers immense potential to improve the human condition, but only with appropriate oversight.
Scientific, regulatory, and governmental agencies are starting to get involved at the national level. In the United States, for example, the US Department of Agriculture has begun informing some food producers how gene-edited crops will be regulated, and the National Academies of Sciences, Engineering, and Medicine have authored studies on human gene editing and gene drive technology that include comprehensive sets of recommendations for future uses and oversight. Similar analyses and prescriptions are also being published in other countries.
By placing the power to easily rewrite genetic code into the hands of scientists worldwide, CRISPR offers immense potential to improve the human condition, but only with appropriate oversight.
Moving forward, these discussions and guidelines must extend across national boundaries as well, given the global implications of gene editing.
Take gene drive technology, in which CRISPR-modified animals would be released into the wild, with the intent of spreading traits like malaria resistance. By their very nature, these modified organisms would cross national boundaries and territories, complicating questions of governance, such as who should make decisions about field trials, who should be accountable, and how should liability be handled. In the case of malaria-resistant mosquitoes, careful global engagement would be especially important since the field trials would likely take place in those low- and middle-income countries disproportionately affected by the disease, whereas early research would likely occur in high-income countries like the United States and the United Kingdom.
Proactive and assertive global governance is also an imperative in the controversial area of heritable gene editing in humans. Although the potential impacts would be slower to surface than gene drive technology, uncontrolled advances in certain parts of the world could lead to an international genetic arms race or the emergence of regulatory havens and a “race to the bottom.” A cautionary tale on the risks of inaction can already be seen with a related assisted reproductive technology known as mitochondrial replacement therapy, which is being developed but is not yet clinically approved in the US. In a recent case, however, a New York physician exported genetically modified embryos to Mexico for implantation, specifically to evade US restrictions. Imagine the type of industry that might result if the intent were not to produce an embryo free of genetic disease, but an embryo with a genetic enhancement enabled by CRISPR.
Robust international governance could discourage this kind of medical tourism, assure equal protection for the citizens of all nations, set international gene-editing standards for scientists and companies, and help prevent trade disputes with gene-edited foods. The challenge is determining what mechanism of international convergence is actually possible, given the substantial legal differences that are already in place across the globe on issues like GMOs and genetic modification of human embryos.
Formal regulatory harmonization across the many CRISPR applications, such as would be accomplished through international treaty, is unlikely to be feasible. Different countries exhibit unique social, political, and ethical norms that are often mutually incompatible, and the substantial resources required to arrive at legally-binding agreements are often not justified by the outcomes. For example, despite numerous meetings in the early 2000s aimed at a prohibition of human reproductive cloning, the United Nations General Assembly was unsuccessful in reaching a consensus on a binding convention. In the case of the Cartagena Protocol on Biosafety, which ensures the safe handling, transport, and use of genetically modified organisms produced through biotechnology, over 150 countries are member parties but the protocol has not been ratified by major global players including the United States, Canada, and Argentina.
So what should effective global governance of gene-editing technology look like? A critical first step is transnational policy diffusion, in which regulators and governing bodies from different nations maintain frequent and open lines of communication as technologies develop. An excellent precedent was set with the 2015 International Summit on Human Gene Editing in Washington, D.C., in which scientific agencies from the US, UK, and China acted as co-hosts and another dozen countries were represented by invited speakers.
The next step is looking for ways to strengthen international cooperation and coordination, especially through the involvement and broadened oversight offered by other stakeholders such as NGOs, professional scientific societies, and public-private partnerships. For example, the International Standards Coordinating Body was recently established to create standards for cell and gene-based medicine products, and the International Society for Stem Cell Research has published guidelines for experiments involving genetic changes to human embryos. Also crucial is a reliance on public outreach and engagement to facilitate decision making, so that the multinational diversity of opinions on gene editing’s societal impact becomes an asset rather than an impediment.
Gene-editing technology offers incredible potential to positively transform our world, but only by persistently confronting and addressing its global ramification can we ensure that the benefits accrue to all. As Louis Pasteur once said, “La science n’a pas de patrie, parce que le savoir est le patrimoine de l’humanité, le flambeau qui éclaire le monde”. Science has no homeland, because knowledge is the heritage of humanity, the torch that illuminates the world.
Jennifer A. Doudna is a professor at the University of California, Berkeley, investigator with the Howard Hughes Medical Institute, researcher at the Lawrence Berkeley National Laboratory, and executive director of the Innovative Genomics Institute. She is co-author of A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution.
Samuel H. Sternberg will start as assistant professor at Columbia University in 2018. He is co-author of A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution.