Prof. George Church is trying to clone a woolly mammoth that was trapped in the Siberian ice 52 thousand years ago
She was big, hairy and full in all the wrong places. She shook the ground with every step. People worshiped her, spoke in praise of her, feared her. But she didn't care what they said about her. Her name was Yakinaf, and she lived the good life of woolly mammoths in Siberia, 52,000 years ago.
Then she died, and her body was trapped in the ice and kept in perfect condition to this day. And now, thanks to new and exciting research, she can tell us about the genetic structure of woolly mammoths and the composition of their chromosomes. And maybe, with a little luck, also come back to life in the end.
But let's start at the beginning.
Bring back the mammoths
He stands over two meters tall, with a mane of white hair that joins a broad beard. He was raised in the swamps by a single mother. As he walks, people tremble around him. It is not a mammoth, but Professor George Church - who is also widely known as the Thomas Edison of genetic engineering. Among his many achievements is the development of a method for sequencing the genetic code, which contributed to the human genome project. Oh, and he also started the Human Genome Project sometime in 1984, when most readers were still in diapers at best, or diapering others at worst.
Church's name is associated with Methods with jaw-dropping names, such as molecular multiplexing, homologous recombination and array DNA synthesizers. Based on these and other inventions, several companies were established for genetic engineering and sequencing the genetic code. During his scientific-technological-entrepreneurial history - which is still far from over - he has probably already stopped counting the number of awards he is considered to have won. In short, the man did a thing or two.
And in the last decade he has been trying to revive the woolly mammoths.
Church founded the Colossal Biosciences company in 2021, with the stated goal of bringing back to life the woolly mammoths, the Tasmanian tiger and of course - his uncle. The company managed to raise a good amount of money, which allowed the researchers to advance the field. Thanks to this company, the woolly mammoths may yet return to graze the frozen tundras.
And if you're like me, you're probably asking now with some bewilderment - why?
Why bring back the mammoths?
Why do we even need the woolly mammoths back in our lives?
The first argument is that mammoths can help us stop climate change. The Siberian steppes include large areas that are scientifically known as "super-freeze". The ground in those areas is practically frozen, so that plants find it very difficult to grow on it, and the large herbivores find it doubly difficult due to the lack of plants. This super-freeze is currently in the process of thawing, and if these are successfully realized, the meaning for the climate will be devastating. In the super freeze, three times more carbon is trapped than in all the forests on the planet, and all of it will be released into the atmosphere and jumpstart climate change.
Studies - it is difficult to know for sure how reliable they are - have shown that resettling the tundra with large mammals can prevent the thawing of the super freeze. Mammals such as bison, elk and horses encourage the growth of grass in the permafrost, and the bright grasses reflect sunlight back into the atmosphere, thus slowing the heating of the ground. This means that repopulating the tundra with woolly mammoths may prevent the thawing of the permafrost and delay climate change.
Maybe. This, at least, is the first central argument.
The second main justification - and I suspect it is more relevant to those involved in the craft - is that it's really-cool-and-let's-go-forward-let's-do-it-nobody-has-done-it-before.
And I can have that too.
Regardless of the real reason behind the research, we continue to promote it these days. The company Colossal Biosciences succeeded just recently, they were able to reach a breakthrough and make normal elephant cells turn back into stem cells. The hope is to use these stem cells, among other things, to understand how elephant embryos develop. These insights will serve us in any attempt to bring woolly mammoths back to life, because the genetic similarity between Asian elephants and woolly mammoths stands at 99 percent.
Despite the initial achievements, it is clear that there is still a long way to go. One of the reasons for this is that even if we managed to sequence a significant part of the genetic code of the mammoths, until today we did not understand how their DNA was arranged in space.
They were all chromosomal
You can think of DNA as a rope that contains all the information necessary for a cell to operate, reproduce and make decisions. The DNA contains the plans for the design and growth of the fetus in the womb, as well as the explanation for the way the cells behave inside the body. But it is not just one rope. In fact, we have several dozen such 'ropes' in each cell, each of which is wrapped and curled around itself. We call each of these coiled ropes "chromosomes".
Why are the DNA ropes rolled up and packaged in the form of chromosomes? Well, they have to be packaged in some way! The packaging protects them from premature priming, such as that which occurs with particularly worn shoelaces. Besides, the DNA can be tightly coiled - especially in the regions of certain genes, and then the cell cannot read them. When those genes need to be read and acted upon, the cell has ways of untying the rope at that point, reading the necessary genes, then repackaging them if they need to be 'silenced', or leaving them exposed if they are still needed.
The meaning is that if we want to understand how the genetic code of a certain creature affects the way it is formed in the womb, or even its life as an adult, we must also understand how its DNA is arranged in the chromosomes.
And this is a very difficult task, when it comes to an organism that became extinct thousands of years ago.
DNA tends to be destroyed quickly after death. The long rope unravels, frays and tears at many points along its length, and the cabin and body are filled with short pieces of rope, in one big mess. You can think of the matter as a puzzle that breaks down into millions of pieces - and from some of those pieces the edges that are supposed to connect them were cut. Oh, and some of the pieces were just completely destroyed. Good luck rebuilding the puzzle.
What do you do in such a situation?
In an ideal situation, ancient DNA researchers can rely not on one such puzzle - that is, not on DNA from a single mammoth - but on many puzzles. They harvest DNA from several mammoths, and since in each sample other pieces of the puzzle have been corrupted, they can find the pieces that are the same between the different mammoths through the work of ants. But this does not help them understand the three-dimensional structure of DNA. This remains a blind spot of science. It was clear that a well-preserved DNA sample was needed to try to decipher how the DNA was arranged in the chromosomes in mammoths.
And this is where Yakinaf entered the picture.
Yakinaf's story
Yakinaf lived in the frozen steppes of Siberia 52,000 years ago. To be honest, her life story is probably not very interesting - at least not any more than that of any elephant living today. She was born like a mammoth, ate like a mammoth, and one can hope that she was also blessed to have offspring like a mammoth. What's important is that when she died, she was thoughtful enough to do so in such a frozen environment that her cells didn't go through cycles of freezing, thawing, and refreezing.
why is it important? Because each such cycle of freezing and thawing causes severe damage to the DNA. Most woolly mammoths were not as thoughtful as Yakinaf, and the only parts of them that have been well preserved are the tusks (which sell on the market for $250,000 per tusk). But Yakinaf - Yakinaf knew how to die properly. You can even find hair samples on her skin, and whole hair follicles are found in the skin tissue. But the most important thing is that in Yakinaf's cell it is possible to find large pieces of DNA, which the freezing process preserved in good condition.
And that's a good start to research.
In recent years, a whole group of researchers, led by Erez Lieberman-Eiden from the Broad Institute of MIT and Harvard, has been working diligently to decipher how the pieces of Yakinaf's DNA joined together into chromosomes. They used an innovative method called Hi-C, which makes it possible to decipher what the DNA looks like in its three-dimensional form. This method works well in modern organisms, but no one knew if it would also work on 52,000-year-old DNA. It took Lieberman-Eiden and his team five years to track down Yakinoff's frozen body and decide that she was the woolly mammoth they were looking for.
Yakinaf did not disappoint.
A well-preserved hairy leg of a woolly mammoth. Source: ABC News, who received the photo from Lab Dalen at Stockholm University
the research, Published in July 2024 in the respected scientific journal Cell, describes the miracle performed by the researchers, with the generous help of Yakinaf. They discovered that the DNA of the woolly mammoth was arranged in 28 chromosomes, Similar to the number of chromosomes of Asian and African elephants today. And that was just the beginning, as they were able to understand for the first time how the DNA structure was responsible for turning certain genes on and off in the mammoth. They identified, for example, that genes responsible for adapting to the cold, or for creating hair, were activated in the mammoth cells. In elephants? much less. And these are just the initial results of groundbreaking research. What else will we discover in the future about mammoths? We will have to wait and see.
But before I close this entry, I want to say what excites me personally about the current discovery. The mammoths, their dignity is in place, but we are still far from bringing them back to life. The really important thing here is that we have a method that can help us discover more information about the ancient animals. This method may not help us learn about the ancient lions in hot Israel - where the DNA breaks down even before the organism dies - but we can hopefully use it on the bodies of other animals in colder regions.
And why stop at animals?
The Denisovan man became extinct forty-thousand years ago - about the same time that Yakinaf returned her soul to the glacier. This is a population that split from our ancient ancestors, and whose genetics were different from ours. He lived in Siberia, and even had common descendants with the humans of today. What can we learn about him, thanks to techniques like Hi-C to discover the original three-dimensional structure of his DNA?
To be clear: I am not proposing to bring Homo Denisovans back to life. But it amazes me to think that we can understand our ancestors, our cousins and even the primitive animals at the resolution of the smallest molecules, tens of thousands of years after they became extinct. Thanks to the combination of science and technology, we can understand the past better than ever, and even know how the genes were activated in cells that lived many thousands of years ago.
And science and technology will only continue to advance. As I have been saying for more than 15 years, and will continue to say as long as I breathe: this is only the beginning.
