My Interview with Mark Thomas on Woolly Mammoth De-Extinction

This is honestly a Columbian, rather than woolly, mammoth.

These are notes from my interview with Dr. Mark Thomas, a scientist who has done some excellent work on mammoth genomes. This interview was conducted while I was working on my feature for The Washington Post about problems with bringing woolly mammoths back from extinction.

You were involved with some of the earliest research into mammoth DNA back in the early 1990's. To what extent have you kept up with what is happening in that field?

The last paper I published on mammoth DNA was 2005. That was with the advance. So I watched on the genomic stuff. I've watched it a little bit. But they are doing it from an ancient DNA to analyze details for its evolution. I'm aware that George Church has been taking some, building genomes, approach like that. I'm not completely up to date on the technologies that he has advanced. He is not, as I understand, a kind of press-hungry bullshitter. He's the real thing. If he says he's got technologies to do piece-meal insertions of relevant genes, he's probably got it.

There are a number of approaches you can take to de-extinction. One, you can try to clone a cell. I find it really incredible to imagine that you would have an intact cell from that long ago. If there is a species that you could do it in, it's mammoths. But I still find that difficult to believe. That does not mean that there won't be technologies that can do that in the future. When you have double-strand breaks, most cells don't know what to do with it. In terms of repairing double-stranded breaks on old cells and cloning them up, that is sort of science fiction at the moment.

A second approach, there may be something special about how chromosomes are packaged in sperm. So you could use sperm to cross with an elephant and then back cross until you have a real mammoth. I would still be amazed if you could find a sperm that didn't have a double-stranded break. When you have a double-stranded break, how do you know where to join it back? But there may be some special preservation circumstances. I'm not aware of one...

Do you think that we will ever see mammoth genes functioning in either living mammoths or elephants?

Yes, we will definitely see mammoth genes functioning in elephants. There is no doubt that this will happen. We will definitely see a number of them functioning. I don't want to guess how far in the future but it will happen. Maybe sooner rather than later. Undoubtedly we will see functionally important genes in an elephant that has some mammoth appearances.

The funny thing would be if you did everything but the teeth...

Adrian Lister doesn't think its a good idea..

The Riken Center published a paper back in 2006 announcing that they have cloned mice that had been frozen for 16 years without any special preparation. Since that time, nobody has duplicated those results. Are there any red flags here that should cause people to question the research?

Yes. Of course there are red flags. There are always red flags when it hasn't been replicated, especially for such an interesting target for research. I remember reading it when it came out and thinking, 'really'? We tend to be healthily skeptical when its published in a respectable journal. I still remain today to be surprised. …which does make the whole thing smell a little bit worse. It's not my natural gut reaction to say 'you're wrong' but we tend to hold a lot of things in the cloud of uncertainty.

It's interesting that nothing's been replicated. The fact that the second in command of the lab turned out to be a dirty crook, that makes me even more skeptical. That doesn't mean that I dismiss it entirely.

George Church claims that he has a line of elephant cells living and growing in his lab right now that contain 14 mammoth genes associated with survival in cold weather. However, he has not published a paper about this in a peer-reviewed journal. He is unable to direct me to an independent laboratory that can confirm his claim. Would the mainstream scientific community consider this an acceptable way to conduct and announce research?

There's two things here. So firstly, as far as I'm aware, George Church is a highly credible scientist who is extremely unlikely to make something like that up. Secondly, its an impressive achievement but its not shocking. He's one of the world leaders in, sort of, in synthetic DNA. I would have absolutely no reason to disbelieve that. He's going to get excited about it. It doesn't sound to me like he's gone to the press with this. No I don't think that there's anything wrong with him telling you about that.

It may have smaller ears, it may be furry, it may have some mammoth tooth morphology. Its not a mammoth. It's an elephant with mammoth genes, but it ain't a mammoth.

The third approach we can take is that you build up the genome piecemeal. He is a world leader in that kind of technology. It seems perfectly reasonable. It doesn't sound like a false claim or anything. We don't even know what most of the genome does.

...the RNA genome is seen as increasingly important. Now maybe there are no differences between the RNA of a mammoth and an elephant. We don't know.

It's essentially taking some steps on a path. There is a route to de-extinction. It's a long route, but it's there.

George Church claims that 'gestation without implantation' will be possible in a laboratory setting in time for him to clone a mammoth without using a surrogate mother at all. What is your opinion of this claim?

In the words of one of your politicians, 'there are the known unknowns and there are unknown unknowns'... we are only beginning to learn about how vast and... there are a lot... so he may know something I don't know.

Take a step backwards. I would have thought he would have given a better answer to that. Yes, those early experiments were difficult. No doubt the number of tries are going to come down so there's that. I think he's using a sledge hammer to crack a nut. Maybe, maybe someones got that around the corner as well. No doubt were going to make it a less wasteful process.

What do you see as the primary technical barriers to creating a living mammoth?

When it comes to cloning a mammoth, just DNA damage. When it comes to constructing a genome, it's just a lot of work. Even with today's technology it's just a lot of work. George Church is the leader in the field. 14 genes, that's impressive. But its only a very small drop in the ocean.

In the next few decades, do you think that it will eventually be possible to synthesize a mammal, such as a lab mouse, by artificially generating a genome, putting it into an enucleated cell, and growing it in a surrogate?

By that specific route, artificially making DNA, putting it into a cell and hoping it forms chromosomes, no, not in the next 20 years.