Modelling early human development

16 June 2020

Interview with 

Alfonso Martinez Arias, University of Cambridge

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In order for us to be talking to you today, and for you to be listening, an incredibly complex cascade of events took place during our mothers’ pregnancies. There’s so much still to be understood about human development, and this week news is out of a model that could give scientists much better insights into how we come into being. Alfonso Martinez Arias from Cambridge University is one of the scientists behind a new model, which they say will allow scientists to probe the processes of early human embryonic development in the lab for the first time. They’re modelling an early developmental stage called gastrulation, where different parts of the body start to form. This is poorly understood in humans owing to restrictions around growing embryos for research beyond 14 days. So what exactly is this model, and what can we learn from it? Alfonso spoke to Katie Haylor...

Alfonso - What we have achieved on the plate is a simulation of the process of gastrulation. Now this is a mouthful of a word for many of the people listening, but as a biologist said, the most important moment in your life is not when you're born or when you get married or when you die. It's when you undergo this process of gastrulation. So before explaining what it is that we have achieved, it's important to get the perspective of what this process is. During these magical event, the ball of cells that results from the fertilisation of the egg, it transforms itself in a very origami sort of way into the outline of an organism, with the seat of the head at one end and behind it, the heart and the gut and the muscles and the bones. This is a process that happens deeply inside the uterus. It has never been observed in the lab, in reality. And we have managed to reproduce it in the lab.

Katie - How have you done this then, if it's so difficult to do?

Alfonso - One of the things that has opened up the way for these kinds of experiments is embryonic stem cells. Embryonic stem cells are cells derived from early embryos that can be kept in the lab indefinitely and can be enticed to differentiate into different cell types of an organism. But they had never been put together or attempted to build the rudiments of an organism with that. We found the way to entice them, if you wish, to come together in a way that they are able to undergo this process in the dish and outline the organism, the little human being. I should point out that at these earliest stages, the human embryo is about one or two millimeters long, which is the kinds of object that we obtained with the cells.

Katie - Wow. Why hasn't this been done before though? Can you tell us a bit about the ethics around this kind of work?

Alfonso - Yeah, it is important to highlight that we know a lot about this process in many, many animals and even in mice. But it has never been achieved in humans. And the reason for that it has to do with something that is called the 14 day rule, which was set up during the studies of in-vitro fertilisation, when people realised that you could grow early embryos in a dish, but then that raises the point of how long could you keep these embryos grown in the dish? A committee was set up, run by Mary Warnock, and in that committee, they decided that the point at which you could never grow embryos longer in the dish was day 14. Why? Because that's the day at which this magic process of gastrulation happens. In any case, this process takes place very deeply inside the uterus. And therefore has never been observed before. These days, there are people growing embryos in the lab, but they have technical difficulties to get them beyond this day 14. We have managed to find a way which does not exactly reproduce the early events of the embryo, but it produces the process of gastrulation. And it yields the structure of these early embryos.

Katie - I see. So would it be fair to say that this model wouldn't result in an embryo, if you were to continue the model?

Alfonso - That is indeed very, very important. There are two features of our system that are present in embryos and that we have managed to avoid in the way we treat the cells. One is the appearance of a brain. That doesn't mean that the system does not have a nervous system. There is more to the nervous system than the brain. And we have the seeds for the neurons in our system. And it also lacks a set of cells that allow the embryo to attach to the mother. Therefore, the system that we have would never develop into a full embryo at the moment.

Katie - I see. And just briefly, what are you hoping to learn? Or you're hoping the field will learn this model?

Alfonso - There are three things. One - as a scientist, this is the first time that we can actually see how gastrulation happens in a human embryo and compare it to other animals. And this is one of the things that we do in the paper. Second - most importantly, there are many birth defects that probably have the roots in the process of gastrulation and that has never been able to be studied. With the advent of these IPS cells, induced pluripotent stem cells, you can make now embryonic stem cells from patients with these diseases. And we could try to model them, to copy them and ask how do they produce, how do they go through this process of gastrulation? Finally, I think it would be a very good system for drug screening of substances that people might want to test for pregnancies, and how would they affect the earliest stages of human development.

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