Monday January 19 2015
Will we be able to create babies free of disease?
"Rapid progress in genetics is making 'designer babies' more likely and society needs to be prepared," BBC News reports.
The headline is prompted by advances in “DNA editing”, which may eventually lead to genetically modified babies (though that is a very big “may”).
The research in question involved the technique of intacytoplasmic sperm injection (ICSI), where a mouse sperm cell was injected into a mouse egg cell. At the same time, they injected an enzyme (Cas9) capable of cutting bonds within DNA, alongside “guide” RNA to guide the enzyme to its target location in the genome. This system then “cut out” targeted genes.
So far, the techniques have only been tested in animals and for “cutting out” very specific genes (currently, under UK law, any attempt to modify human DNA is illegal).
Although this is very early stage research, the potential uses could be vast. They range from arguably more “worthy” uses, such as editing out genes linked to genetic conditions such as cystic fibrosis, to opening up the possibility for a whole manner of cosmetic or “designer” uses – such as choosing your baby’s eye colour.
Such a possibility is always going to be controversial and lead to much ethical debate. As the researchers say, the possibility that these findings could one day lead to similar tests using ICSI techniques in human cells suggests that it is time to start giving this careful consideration.
Where did the story come from?
The study was carried out by researchers from the University of Bath and was funded by the Medical Research Council UK and an EU Reintegration Grant.
The study was published in the peer-reviewed scientific journal Scientific Reports. The study is open access, so it is free to read online or download as a PDF.
The BBC accurately reports this study, including quotes from experts about the possible implications.
What kind of research was this?
This was laboratory and animal research, which aimed to explore whether the DNA of mammals can be “edited” around the time of conception.
The researchers explain how recent study has developed the use of an enzyme that cuts bonds within DNA (Cas9). This enzyme is guided to its target location in the genome by “guide” RNA (gRNA). To date, the Cas9 system has been used to introduce targeted DNA mutations into various species including yeast, plants, fruit flies, worms, mice and pigs.
In mice, Cas9 has been used successfully to introduce mutations in single-cell embryos, called pronuclear embryos. This is the stage where the egg has just been fertilised and the two pronuclei – one from the mother and one from the father – are seen in the cell. Such early targeting of the embryo’s genome directly leads to an offspring with the introduced genetic mutation.
However, it is unknown whether Cas9 and gRNA could be used to introduce genetic change immediately before the pronuclei are formed (that is, when the sperm cell is fusing with the egg cell, but before the genetic material from the sperm has formed the paternal pronucleus). Therefore, in this study, the researchers aimed to see whether it was possible to use Cas9 to edit the paternal mouse DNA immediately following ICSI.
What did the research involve?
Briefly, the researchers collected egg cells and sperms cells from 8-12 week old mice. In the laboratory, the sperm were injected into the egg cells using the ICSI technique.
The Cas9 and gRNA system was used to introduce targeted gene mutations. This was tried in two ways: firstly, by a one-step injection, where the sperm cell was injected in a Cas9 and gRNA solution; and secondly, where the egg cell was first injected with Cas9 and then the sperm was subsequently injected in a gRNA solution.
The sperm cell that they used had been genetically engineered to carry a certain target gene (eGFP). They were using the Cas9 and gRNA system to see whether it could “edit out” this gene. Therefore, the researchers examined the subsequent stages of blastocyst development (a mass of cells that develops into an embryo) to see whether the system had introduced the required genetic change.
They followed the studies targeting eGFP with studies targeting naturally occurring genes.
Resulting embryos were transferred back to the female to grow and develop.
What were the basic results?
Following ICSI, around 90% of fertilisations developed to the blastocyst stage.
When the researchers first carried out a fertilisation using the male sperm that had been genetically engineered to carry the eGFP gene, about half of the resulting blastocysts had a functioning copy of this gene (i.e. they made the eGFP protein). When the sperm were simultaneously injected with the Cas9 and gRNA system to “edit” this gene, none of the resulting blastocysts showed a functioning copy of this gene.
When they next tested the effect of pre-injecting the egg cell with Cas9, and then injecting the sperm cell with gRNA, they found that this was also effective at editing the gene. In fact, subsequent tests showed that this sequential method was more effective at “editing” than the one-step injection method.
When the eGFP gene was introduced into the egg cell rather than the sperm, and then the Cas9 and gRNA system introduced in the same way, only 4% of the resulting blastocysts demonstrated a functioning copy of this gene.
When next testing the naturally occurring genes, they chose to target a gene called Tyr because mutations to this gene in black mice resulted in a loss of pigment to the coat and eyes. When the Cas9 and gRNA system was similarly used to target this gene, loss of pigment was transmitted to the offspring.
How did the researchers interpret the results?
The researchers conclude that their experiments show that injecting egg cells with sperm, along with Cas9 and guide RNA, “efficiently produces embryos and offspring with edited genomes”.
This laboratory research using sperm and egg cells from mice demonstrates the use of a system to produce targeted alterations in the DNA – a process the media like to call “genetic editing”. The editing happened just before the genetic material of the egg and sperm cell fuse together.
The system makes use of an enzyme (Cas9) capable of cutting bonds within DNA, and a “guide” molecule targeting it to the correct genetic location. So far, the techniques have only been tested in animals, and for “editing out” a small number of genes.
However, though this is very early stage research, the results do unavoidably lead to questions about where such technology could lead. ICSI techniques are already widely used in the field of assisted human reproduction. ICSI is where a single sperm is injected into the egg cell, as in this study, as opposed to in vitro fertilisation (IVF), where an egg cell is cultured with many sperm to allow fertilisation to take place “naturally”.
Therefore, the use of ICSI makes it theoretically possible that this study may one day lead to similar techniques being possible to edit the human DNA around the time of fertilisation and so prevent inherited diseases, for example.
As the research importantly states: “this formal possibility will require exhaustive evaluation”.
Such a possibility is always going to be controversial and lead to much ethical and moral debate over whether such steps are “correct” and where they could possibly then lead to (such as altering other non-disease aspects of inheritance, like personal traits).
As one of the lead researchers reports to BBC News, extreme caution will be needed with any further developments. However, they consider that the time is right to think about this, as it is an issue that the UK’s Human Fertilisation and Embryology Authority (HFEA) – the body that monitors UK research involving human embryos – is likely to have to face at some point.
While the possibility of DNA editing in humans may seem like the stuff of science fiction, our Victorian ancestors would have felt the same way about organ transplants.
A spokesman for the HFEA is quoted in BBC News as saying: “We keep a watchful eye on scientific developments of this kind and welcome discussions about future possible developments…It should be remembered that germ-line modification of nuclear DNA remains illegal in the UK”. They say that new legislation would be needed from Parliament “with all the open and public debate that would entail” for there to be any change in the law.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.