Cloning a Mammoth is Only the Start

It’s the spin-offs that matter, says molecular biologist Kevin Campbell—the technological breakthroughs that can help humans too.

Apr 6 2015, 5:00pm

​Image: ​Brett Burton/Flickr

Earlier this year, Motherboard visited the lab of Sooam Biotech, a South Korean company that has been working to clone a woolly mammoth from preserved tissue samples and blood. But just how likely is the mammoth's revival? ​Molecular biologist Kevin Campbell, a professor from the University of Manitoba, shared his thoughts.

A South Korean biotech firm says it's well on its way to cloning a whole mammoth. What do you think about that?

It's not gonna happen. Never a true clone. There are so many technological hurdles that have not yet been cleared.

One, what they're trying to do is get a perfect cell from a mammoth—take the DNA out and put it into an elephant egg. Well, DNA is a very fragile molecule. Very, very fragile. A single chromosome is hundreds of millions of base pairs, chemical bonds that are put into a little pearl necklace. In our bodies, these little bonds are broken all the time, millions of times a day. We've got all these enzymes that fix that. Well, mammoths have no enzymes to fix that. So you'll never find an intact chromosome.

I've put it like this before: I have a beautiful little ceramic vase. I put a flower in it for my wife. I come back a few hours later and there's a puddle of water around it. So, it looked perfect, but it has all these tiny little cracks we can't see.

Can we fix it? Maybe. But fix it to what? We don't know what their chromosomal arrangement was. We would first have to figure this out before we could synthesize them.

Then, we have to take an egg out of an elephant somehow and put a modified one back in. Nobody's ever done that. It's possible, but it would take a lot of attempts. Elephants don't ovulate that often. To get that many eggs? That's a problem. And then you have to wait 20 months! Just to see if there's something viable.

Another major problem is this egg will be full of elephant proteins. Most importantly, it has elephant mitochondria—the little powerhouses—which have their own DNA. So any offspring will be a chimera between an elephant and a mammoth because it's going to have elephant DNA. This may cause some problems because it's a different kind of powerhouse that may not work well inside the mammoth cell.

The biggest kicker: Even if they manage to overcome every one of these hurdles somehow, mothers and fetuses communicate constantly during gestation. And these communications turn on and turn off specific pathways that alter development. All you need is for one miscommunication and development takes a different path and leads to a natural abortion. These kinds of things happen all the time in humans and other animals. A huge number of pregnancies end up in spontaneous natural abortions— reabsorbed by the mother or stillborn.

But if there's enough will, like going to the moon in the 1960s, somebody might do it.

So why are we doing this?

I think there are lots of good reasons, actually. Take going to the moon. The hurdles of going to the moon were immense. And that led to new technological breakthroughs, unrelated to space travel. That's where diapers came from!

To me, the importance of this is not to build a mammoth or sabre-toothed cat or passenger pigeon. The importance is the spin offs—the new technology that can be used for other purposes. That's why we should try.

Your research involves genetic products, such as proteins, obtained from extinct mammalian species like mammoths. What can we learn from these ancient materials?

Mammoths spent most of their evolutionary history in Africa—about 4 to 5 million years. We know this from teeth and fossils. 1.8 to 2 million years ago, just as the ice ages started, these animals moved up into the arctic [where] there's this sudden selection pressure. We know that because these animals changed dramatically. They got this thick pelt, their tails got smaller, body shape changed. So, mammoths are a nice model to understand potentially important DNA changes [to adapt] to this new climate.

DNA mutates all the time. But the bigger the species, the longer the lifespan, the slower all that change occurs. Mammoths probably have 300,000 [genetic] changes. So what we can do is target specific genes and we can look for these changes. Then, we can synthesize the proteins for those genes and compare how the proteins actually work.

Take the mammoth's hemoglobin. We expected it to have different properties that would allow it to offload oxygen at cold temperatures. Feet, ears, extremities. You need oxygen to be delivered there. We found two genetic changes that would have aided in offloading oxygen in cold temperatures. We don't need a breathing mammoth to do the work that we do.

Could we tailor these findings for use in our own bodies?

Oh yeah, sure! Most of the processes that go on in your body every second, you're completely unaware of. They're very complex. We have a good understanding of how it works, but we don't know precisely the role that every single building block does. And why it works the way it does.

So for certain things, like hemoglobin and blood, it would be nice to engineer specific properties for medical purposes. For example, our hemoglobin, does not work well at cold temperatures. It binds oxygen really tightly. Whereas mammoth [hemoglobin] works appropriately at warm and cold temperatures.

With heart attacks, strokes, spinal cord injuries, an emerging procedure is called a hypothermia-dependent procedure. What they do is they drop people's body temperatures right down. Induce a coma, pack ice around their hearts and spinal cord. The problem with that? Our hemoglobin doesn't work well at that temperature. So ideally we'd like to make a blood substitute! Blood that works at cold temperatures.

Another use could be transplanting hearts. These hearts, outside the body, they're not getting oxygenated properly. If we can engineer [cold-effective hemoglobin], that would help.

So these are applications that can be used from these animals. They've worked it all out. Evolution has figured out these problems and what we're trying to understand is how these specific changes alter protein functions.

This interview has been edited and condensed.

Orphan Black returns April 18th 9e/10p on Space. Catch up now