How does a human develop?
Whether you can conceive naturally or get help from fertility specialists, hopefully the end result is a healthy baby, 40 weeks later. But how does a fertilised egg turn into a baby? Chris Smith went to see expert in human development at Cambridge University’s Gurdon Institute Azim Surani, who was doing his PhD with IVF pioneer Bob Edwards 40 years ago...
Azim - I remember the day when Louise Brown was born. I was actually on holiday in Cornwall, and I heard the news and I sent a telegram to Bob congratulating him.
Chris - No email in those days?
Azim - There was no email in those days so I had to send him a telegram.
Chris - Let’s go right back to the beginning of the life process which begins with sperms and eggs. So what is special about those two cell types that makes it possible for them to give rise to an embryo and then a foetus and a baby?
Azim - The egg and sperm only contain half the number of chromosomes, so they only have half the information for making a whole organism. And you need to fertilise an egg so that you have both sets of information from father and mother; that’s when the process of development can start.
Chris - How does the egg “know” it’s been fertilised?
Azim - Well, at fertilisation there are changes in the levels of some chemicals like calcium in the egg, and that actually starts the process of early development. That’s when the egg starts to divide and starts to develop further.
Chris - If you’ve got millions and millions of sperm competing to fertilise the egg, why is just one successful?
Azim - Yes, this is actually very important. Because what happens at fertilisation is as soon as one sperm enters the egg there are changes in the membrane of the egg which prevents further sperm from getting in. This is actually very important because you need exact numbers of chromosomes from each of the parents. If you have too many from the father then the process of development will go array.
Chris - So sperm gets into the egg, triggers this change in the membrane preventing any other sperm getting in. It then gives its genetic cargo to that egg so we’ve now got a cell with, hopefully, a complete assemblage of chromosomes - 23 pairs of chromosomes. Then what happens?
Azim - This is the point when the egg starts to divide, and it divides into two cells first. Then it continues to divide as it travels down the fallopian tube and enters the uterus, and, as it divides, the cells continue to multiply. They go through a number of divisions until the embryo reaches about 60 to 100 cells.
Chris - What’s special about that number?
Azim - Basically, there are two sets of cells: there are cells on the inside, which are called the inner cell mass cells which are going to give rise to the embryo, and then there’s the outer shell of cells which will give rise to the placenta.
Chris - So we’re at this stage where we have a ball of cells inside a ball of cells. The ball round the outside is going to be the bag that the baby develops in and the placenta that connects it to its mum. But how does that ball of cells in the middle turn into something we would recognise as a developing baby?
Azim - Well, one of the early things that happens is that the embryo starts to look like a sheet of cells, and at one end of the embryo you start to form a little structure called the “primitive streak.” Here the cells start to enter into the primitive streak and they go inside, and those cells are eventually going to give rise to the structures which we recognise as the internal organs eventually, and then it starts to be recognised as a developing foetus.
Chris - So cells are flowing in from the outside into the inside? It’s almost like inflating itself with more of its own cells and it creates that population of cells inside itself which they they're destined to become the internal organs and so on?
Azim - Yes. These cells, they start to become more specialised, as the embryo develops, becomes three dimensional, and it starts to be recognised as a foetus.
Chris - But then what happens next to actually turn this very primitive, very tiny, one millimeter structure into something which would resemble a baby?
Azim - The key aspect that occurs from then onwards are increasing numbers of cells and also increasing complexity of the developing internal organs.
Chris - By which time are all the major organs developed - things like the heart, brain, face, eyes? When are all the major things made and when are they present by?
Azim - The early stages of organogenesis are occuring between day 28 and 35 days of human development. This is when all the rudimentary organs are already formed, so all the basic structures start to get established by this time, and then thereafter there is tremendous growth of the embryo as development progresses.
Chris - Are we comfortable that the manipulations that are being done on sperms, eggs, and embryos to do things like IVF don’t have consequences for the health of that individual?
Azim - From all the experience we have had from all the IVF babies that have been born there is, at the present time, no clear evidence that there is an impact of IVF. Now we have to remember that Louise Brown is 40 years old, so it’s still quite early days. So I think it’s something that we should actually keep an eye on, to see if there are very long term consequences of IVF.
Chris - But at this stage we’re not aware of any?
Azim - There have been a number of experiments that have been done to test if there have been any effects of manipulation of the eggs and sperm in culture. But so far the majority of the evidence is that there’s no potential impact of manipulation of eggs and sperm in culture.
Chris - And last Azim, after you returned from your holiday having sent that telegram to your supervisor, Bob Edwards, what happened next?
Azim - I came back to Cambridge and we had a lot of celebrations. A lot of champagne was drunk I have to say.