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MILLION DOLLAR VIALS

The greatest ethical challenge to genome editing research isn't designer babies, but economics.

Enya O’Connell-Hussey is a research communications officer at Trilateral Research Ireland, with a background in zoology and science communication.

Year on year, the records for the most expensive medications in the world are being broken by a new frontier in medicine — gene therapy.

It sounds like the stuff of the future: gels that deliver packages of genes into cells, one off-shots that grant years of life to patients and IV drips altering the material within our cells. Chronic, debilitating genetic diseases could be made manageable with a single vial of a gene therapy treatment. Yet, most of these treatments cost upwards of a million dollars a dose.

Now, a wave of therapies is in the pipeline. CRISPR-Cas9 technology makes gene editing easier and more efficient than ever, but what is quickly becoming the most pressing issue is patient access.

Gene therapies are often highly specific to the patient and require complicated manufacturing processes. Therapies have decades of research and development behind them, and also replace regular, expensive medical interventions by improving patient’s symptoms long-term. All of this means pharmaceutical companies can argue a single course of gene therapy priced in the millions is a fair price. But whilst resource-rich nations and insurance companies might be able to strike deals with manufacturers to mitigate the cost to the patient, there are fears that as more gene therapies emerge, with higher and higher price tags, under-resourced public health systems might not be able to sustain access. In Brazil, a congresswoman stated that granting access to a novel gene therapy for muscular dystrophy meant "in order to give to one, you have to take the basics from millions of others."

Right now, CRISPR therapies are still experimental, and the only way to access treatments is though clinical trials. These are concentrated in high-income countries. Patients with genetic diseases are already hearing of successes in trials in high-income countries that could take years to reach them, if at all. As so many of these diseases are degenerative, early access could mean the difference between a child being able to walk or needing a breathing tube for life. This is an acute issue for drug developers and researchers, but one not easily solved.

Enrolment in a clinical trial is not a simple process, and conducting a clinical trial in resource-poor settings needs special ethical considerations that many researchers shy away from. The Declaration of Helsinki that lays out ethical principles for medical research in humans, and the CIOMS International Ethical Guidelines for Health-related Research Involving Human Subjects both state that underrepresented groups should be provided appropriate access to participation in medical research.

However, CIOMS guidelines also state that the benefits of this research needs to be fairly distributed to the population being studied. Research bodies must build local research capacity, health infrastructure and creating post-trial access plans when the governments of resource-poor regions do not have the infrastructure to make the products available themselves. Many gene therapies need high-tech medical equipment, thus complicating the practicalities in settings that may lack even basic supplies like blood banks.

There are also concerns around informed consent, unintentional coercion and ethics dumping. Patients in resource-poor settings may not have access to specialists or pre-existing treatments for their diseases, nor fully understand the language or concepts presented. If a clinical trial for a gene therapy is their first opportunity to access free healthcare, they may subject themselves to gruelling treatments and undue risk against their better judgement. Without active collaboration with local researchers and communities, clinical trials will remain a first-world privilege.

Gene therapy in humans is a new field, and the question of equity is a growing thorn. However, it is clear that without active effort from every step of the research ladder, the cavernous global health inequality will only widen. The European research field is making progress in improving research equity. Horizon 2020 funding has already produced guidance for equitable research partnerships between high and low incomehigh- and low-income settings with the TRUST project, which has seen widescale adoption in academic publishing.

As part of irecs, the University of Central Lancaster, Trilateral Research, and the University of Bonn are creating training material for scientists to specifically identify the research ethics challenges of genome editing technologies like CRISPR. Our work is creating training material for students, researchers and ethics experts themselves. irecs is not only identifying the ethical issues of gene editing itself, but the real-world context of the research. We are addressing ethics dumping, working with marginalised populations and just allocation of resources with evidence-informed teaching materials. We want to equip learners not only to solve immediate problems, but give them the tools to tackle unpredictable issues that will inevitably develop.

With the right tools, we can give researchers the confidence to tackle research inequality head-on. The real ethical question facing genome editing right now is not if it works, but who it will reach.