DNA in human embryos altered for the first time
DNA in human embryos has been altered for the first time in the UK by a team at the Francis Crick Institute as they try to understand what happens after a sperm fertilizes an egg. Understanding that stage in the fertilization process could lead to ways of improving IVF or explain why some women miscarry.
The embryos were modified shortly after fertilization and allowed to develop for seven days.
The researchers are exploring one of the most astounding of transformations.
We have all journeyed from a single fertilized egg to a human being – built from myriad different tissues ranging from bone to those needed to read this page.
The first few steps on that journey are as critical as they are poorly understood.
Breakthroughs in manipulating DNA have allowed the team at the Crick to turn off a gene – a genetic instruction – suspected to be of vital importance.
The easiest way of working out how something works is to remove it and see what happens.
So the researchers used the gene-editing tool Crispr-Cas9 to scour the billions of letters of genetic code, find their genetic target and break the DNA to effectively disable it.
They were targeting a gene called OCT4, which is considered a “superstar” in early embryo development. Its complete role is not understood but it acts like an army general issuing commands to keep development on track.
The researchers used 41 embryos that had been donated by couples who no longer needed them for IVF.
After performing the genetic modification, the team could watch how the embryos developed without OCT4.
Over the course of the first seven days, a healthy, normal embryo goes from one cell to about 200. It also goes through the first steps of organizing itself and handing out specialized jobs to different cells.
The embryo forms a hollow sphere called a blastocyst, with some cells destined to go on to form the placenta, some the yolk sac and others, ultimately, us.
But without OCT4 the blastocyst cannot form. It tries – but implodes in on itself.
From the embryo’s perspective it is a disaster but for scientists it has given unprecedented insight.
It is the first time human embryos have been edited to answer questions about fundamental biology.
Dr. Kathy Niakan, a group leader at the Crick in London, said in an interview that they were quite excited about the possibility that their research would open up. “This is basic research which is providing us with a foundation of knowledge about early human development.”
By deepening understanding of the earliest moments in life, it could help explain what goes wrong in infertility.
During IVF, of 100 fertilized eggs, fewer than 50 reach the blastocyst stage, 25 implant into the womb and only 13 develop beyond three months.
This study alone cannot explain what is going wrong or why some women miscarry.
But by interrogating all the genes suspected of playing a role in our inception, it could lead to new advances.
Dr. Niakan said understanding the key genes necessary in successful embryo development could lead to improvements in IVF technology and could also provide important insights into why some pregnancies fail.
One option for IVF is to have a better way of testing which embryos are going to be successful.
Or it may be possible to boost embryos during IVF by growing them in a different culture media – a fertilizer for fertilized eggs.
These experiments have been legal since 2008 in the UK, where it is possible to manipulate such embryos for 14 days as long as they are not implanted.
But while this application of the technology is answering fundamental questions of science, other research groups are trying to remove genes that cause disease, which is provoking deep ethical debate.
