Scientists create a baby mouse with two biological dads and no mum – are humans next?

This is the first case of making robust mammal egg cells from male cells

Mice breakthrough might bring hope for people who can’t have babies. Stock image

Luke O'Neill

It might seem like the stuff of science fiction, but last week scientists from Japan announced they had managed to create a mouse — not from a female and a male mouse, but from two male mice.

The science behind this development is fascinating, and raises all kinds of interesting questions about the nature of reproduction.

It also might bring hope for people who can’t have babies, or maybe one day allow same-sex couples to have children.

What currently happens when two people have a baby is a sperm combines with an egg. Over the course of nine months the fertilised egg develops into a baby.

The system doesn’t work for some couples, which can be devastating.

A big breakthrough to help couples conceive happened with the development of in vitro fertilisation (IVF). This is where sperm and egg meet up in a test tube, with the now-fertilised egg implanted in the female where it grows into a baby.

In July 1978, Louise Brown became the world’s first so-called test tube baby. IVF won the Nobel prize for medicine for Robert Edwards. His two colleagues who were part of the discovery, Patrick Steptoe and Jean Purdy, had sadly died and so weren’t given the prize with Edwards, since the award can’t be made posthumously.

This was a very worthy Nobel prize, with over eight million babies owing their existence to it at the last count.

It doesn’t work for all couples, however, hence the need for ongoing research — and that was precisely the motivation behind the latest discovery.

How they made the discovery is all about what happens during fertilisation.

Each cell in your body has what are called chromosomes. This is where all your DNA is kept — and remember, DNA is the recipe to make you.

There are 23 pairs of chromosomes. Two of the pairs (one pair in the female and one in the male) are called sex chromosomes. These were discovered in 1905 by scientists Nettie Stevens and Edmund Wilson — two unsung heroes, without whom IVF would not have been possible (because chromosomes are watched very closely in that process to make sure there are no abnormalities).

This illustrates how each important discovery in medicine takes an awful lot of people, often doing work that stretches back decades.

In the case of the sex chromosomes, they determine your sex as male or female when you are born.

Females have two copies of the X chromosome, while males have an X and a Y chromosome. When it comes to eggs and sperm however, there’s a big difference. They are unique in the body because they only have one set of chromosomes — 23 chromosomes each, but not as pairs.

In the egg, it’s the X chromosome, while in the sperm it can be X or Y. I’ll bet you didn’t know that what this means is sperm can be male (which in this context means they have a Y chromosome) or female (meaning they have an X chromosome).​

When the sperm fertilises the egg, it delivers either its Y chromosome (which leads to a male, as it will be XY) or its X chromosome (which leads to a female, because it will then be XX). The sperm provides all its other chromosomes as well, and so the fertilised egg will have 23 pairs of chromosomes, just like every other cell in the body — which, remember, are descended from that fertilised egg.

The trick with having two fathers lay in the fact that males have one copy of the X chromosome. What the scientists did was take a skin cell from a male mouse and managed to remove the Y chromosome, leaving it with one X chromosome. They then ‘borrowed’ another X chromosome from a different male skin cell.

This meant a cell that had been taken from a male now had two pairs of X chromosomes, just like the cells in a female. They then went one step further and managed to turn that cell into an egg cell. This meant removing one of the X chromosomes. For the first time ever, the scientists had created an egg cell from a male cell.

To make this work they used a special chemical called Reversine, which can manipulate chromosomes. Reversine was the secret sauce. The rest was easy. They fertilised the egg that had come from a male with a sperm. They coaxed the fertilised egg to grow in an ovary grown outside the body (called an ovary organoid), and then implanted the embryo into a surrogate mother mouse, just like regular IVF in humans.

“This is the first case of making robust mammal egg cells from male cells,” said lead scientist Katsuhiko Hayashi.

This shows us how wonderful biology is.

Hayashi’s team is now attempting to do the same with human cells.

Because of differences between mice and humans when it comes to eggs and sperm, and because of concerns over safety, Hayashi says it will take 10 years. They plan to test the approach they used here in egg cells from females with Turner’s syndrome — a severe form of infertility, where the X chromosomes are missing or damaged.

What they did here might then be a way to provide X chromosomes to eggs from females with Turner’s syndrome, restoring fertility.

Even in mice, though, what they achieved wasn’t efficient. They made about 600 embryos, but only seven survived. With regular IVF, the number would be five times higher. This raised concerns that the mice might be somehow damaged.

Reassuringly the baby mice were healthy. They lived to a ripe old age and went on to have baby mice themselves. Having two males as their parent brought no deleterious effects, as far as the scientists can tell.

The same team of scientists had previously taken male skin cells and reprogrammed them back into being sperm cells which were then used to fertilise an egg in vitro, removing the need for sperm entirely.

That could well be the future too. No need for a female egg, just an egg made from a male skin cell. And no need for sperm, just sperm made from a skin cell. We could therefore be looking at a world where sperm are no longer needed — which might be just as well, given how precipitously sperm counts are falling all over the world. That’s causing concerns about the survival of our species.

The ethical questions of a baby having two dads will need to be considered, but if it is possible to achieve this in humans, same sex couples who want a baby might well be able to have one. All that will be needed is skin cells reprogrammed back to egg and sperm, some Reversine, and a surrogate mother.

That scenario is a long way off — but when it comes to the science of reproduction, who knows what’s next?

Without doubt, it’s a brave new world.