Behind the scenes: pioneering human stem cell research

Dr Kathy Niakan is a group leader at the Crick. In 2016, she became the first person in the world to gain regulatory approval to edit the genomes of human embryos for research. For this, Kathy is in ‘TIME 100’, TIME magazine’s annual list of the world’s most influential people. Here, Kathy reflects on her recent move into the Crick and gives a flavour of the painstaking work that goes on in a world-leading human stem cell lab.

“I would say that the UK is the world leader in human embryo and stem cell research. A lot of that is due to the pro-active legislation, which provides a protected space where you can focus on developing tools that enable you to address really important questions in human biology.

Being in the Crick has significantly increased our ability to collaborate with clinicians. We’re working with nearby clinics much more directly and rapidly than we could in the past. It’s a two-way learning process: they have embryologists interested in basic research who we can learn from as they’re experts in certain aspects like handling embryos. And this can only mean one thing – faster progress.

My interest is in how we start off as a one-cell embryo and the subsequent events that distinguish the cells from each other as they multiply. Increasing our understanding of this fundamental area of biology will, we hope, help uncover pioneering new ways to tackle infertility, miscarriages, developmental disorders, as well as support the development of new therapies using stem cells.

We know a little about the molecular mechanisms in the mouse, but in the human we know very little – the more we compare the two, the more we see how different they are. The classic developmental regulators abundant in the mouse zygote are absent in humans, and vice versa. It would have been so easy if molecularly they had been similar, but they’re fundamentally different at this stage.

Unfortunately, we don’t always have the tools readily available to enable us to test whether insights found in model organisms translate in humans. For example, it wasn’t clear whether CRISPR, which we successfully use to edit genomes in mice embryos, could be used in a human embryo. There were no optimised protocols, so we’ve spent almost a year optimising every single one of the parameters and developing new technologies. We’ve been testing them in any cellular context we can, so before we do anything with even one human embryo, we’ve developed the best methods we can.

Overcoming technical challenges will hopefully enable us to use this technology to address fundamental questions, such as how are the first lineages specified in humans, how do these early cells diverge in their fate and function at this critical stage of development. It’s a really hard choice for IVF patients to decide what to do with excess embryos, so it would be disrespectful to them to not use that precious material in absolutely the best way we can.”