Mice cloned from frozen cells

This week, in 1996, the most famous sheep in the world was born. Named after Dolly Parton, because her co-creator Ian Wilmut used an udder cell to make her, Dolly the Sheep was a giant leap forward in the field of animal cloning. And this week, right on cue, scientists in Japan have taken the technique used to make Dolly - which involved removing the DNA from a skin cell and inserting it into an egg cell deprived of its own DNA - and worked out how to make this process work with cells that have been freeze dried. This means, by banking cell samples from endangered species across the world, we could have a way of safeguarding species that are most at risk. Geneticist Alena Pance, from University of Hertfordshire, took a look at the paper describing the work for us...

Alena - It is mainly about using freeze dried, preserved cells to create new individuals. The main objective was to provide a way to preserve species and recover some of the species that are in great danger of extinction.

Chris - I thought we could sort of already do that because we even do this for human cells. Don't we store sperms, eggs and even whole embryos in freezers? And the law says we can keep them for decades and think they're all right, doing that.

Alena - Yes, but it is extraordinarily costly because it has to be very low temperatures. It's not just like the common freezer at home, which goes to about minus 20. It has to be minus 190, very low temperatures. And it's very costly to keep these conditions. And also they are very vulnerable because if anything happens, we run out of liquid nitrogen, there is a power cut, then all of these samples can be lost.

Chris - Got it. So if we've got cells that are any old cell from an animal and we freeze dried it, so it's a bit like the jar of coffee in the cupboard. It's not gonna go off at anything like the rate that something that has to be on liquid nitrogen is, so it means it's a safeguard for the future and it saves money.

Alena - It is indeed. And it allows to store particularly the genetic material, because what happens is that when cells are freeze dried, the cell dies, but the genetic material in the nucleus is preserved and that can be then revived and an organism can be created from it. And that's the importance of the process.

Chris - Talk us through what they actually did then and how they proved that that is the case in this paper.

Alena - So they have taken skin cells from mice, freeze dried them and stored them at minus 30 degrees. And then from these cells that are dead, they extracted the nucleus, which is where the genome, the genetic material is stored and transferred that nucleus into an egg from which the original nucleus was removed. And from that, they were able to generate mice pups and these mice pups were healthy and fertile and so on. Therefore they demonstrate that this approach can be used to preserve species.

Chris - What was their success rate with this? How many cells did they have to start with and do this on before they got mice back?

Alena - The success rate is very low as with any cloning procedure. They were able to improve their success rate by going through a second cycle. So the nucleus was first transferred, left to develop to a certain stage. And then from that cell lines were generated and then a nucleus from those lines was again, transferred into a new egg. And that increased the efficiency to about 1% to 7% from about 0.02%.

Chris - So it is quite an unlikely success rate, unless you go through this process, do we think that the animals arising from this process are gonna be fit and healthy though? Because I mean, you acknowledge that they appear to be okay and fertile, but are we sure that they're all right, because you can't ask a mouse to do an IQ test to see if it has some kind of mental decrement or something. We have a very limited pool of animals that have been studied here. So is there not the possibility that we have in some way, genetically damaged these animals and that in fact, although the aims are laudable, getting back rare species or safeguarding the future of rare species, we could end up with a very narrow damaged genetic repertoire if we did this?

Alena - So there are several things to consider here. One is that this sort of thing has been tried before, 20 years ago, really. But again, the success rate in those cases was very low. And actually what happened was that most of the babies in this case, it was sheep, died. So clearly they had health issues. In this case, of course it's a small sample, but there were 75 pups that they managed to get. And those appeared healthy. They grew all the way to adulthood and they were able to reproduce.