Scientists Revive 28,000-Year-Old Woolly Mammoth Cells in Mice

The dream of resurrecting species like the woolly mammoth via genetic engineering is old enough that I remember reading articles about it in school 30 years ago. We may never be able to recover enough pristine genetic material from an intact woolly mammoth to make that approach feasible, but scientists working on the remains of the frozen mammoth known as Yuka have taken an incredible step nonetheless, demonstrating that at least some cell functions can remain intact after nearly 30,000 years.

Yuka, found in 2010, is a juvenile woolly mammoth, considered to be the most intact and well-preserved mammoth ever found. That was critical to the researchers’ efforts — earlier tests in 2009 with a less-well-preserved but younger specimen at 15,000 years old yielded no positive results at all.

To be clear: The scientists in question were not able to bring Yuka’s cells back to life. After removing 88 nucleus-like structures from Yuka’s cells, they injected these structures into mouse oocytes — eggs — to see if they could be coaxed back into biological activity. While the cells ultimately failed to divide, they did undertake some of the steps required for cell division, such as spindle assembly. This spindle assembly process ensures that chromosomes are properly prepared to divide before the parent cell actually splits.

Researchers observe biological activity after transplanting cell nuclei from Yuka the woolly mammoth (dead for 28,000 years) into mice oocytes. Whoa! Paper: https://t.co/3kVI5uiGso pic.twitter.com/D6x3TH84zq

— Steve Hurst (@hurst_sj) March 12, 2019

The fact that the cells were unable to fully divide isn’t surprising. The degree of genetic damage inside Yuka’s body was enormous, and while the researchers attempted to find the least-damaged cells possible, none of the samples they ultimately chose were able to completely reactivate.

The research team was able to identify certain biological markers inside the oocytes implanted with mammoth DNA and create a ratio that indicated how damaged the mammoth nuclei were to start with. They labeled this the DNA Damage Index (DDI) with a DDI of 1.0x being equivalent to the overall level of damage observed in fresh mouse sperm. The DDI of the mammoth nuclear varied considerably, from a little more than 1x to nearly 4x. A comparison of the lowest and highest-damaged nuclei is shown below (f). We’ll talk about (i) below.

The (i) graph shows how the DDI ratio changed after the oocyte cells were activated. In most cases, the level of damage increased over time. But in a few cases, the observed DDI level dropped, or at least dropped significantly for a short period. This indicates that DNA repair mechanisms in the mouse oocytes may have activated in response to the damaged nuclei. This does not mean that plugging a 30,000-year-old mammoth nucleus into a mouse egg cell is ever going to result in a fully functional mammoth genome popping out the other side — but it does indicate that the repair mechanisms inside the cell were active and attempting to stitch double-strand breaks in the DNA together. This means that enough DNA existed, in at least rare instances, for the cell to recognize that it was dealing with DNA in the first place, and to have some idea of how to connect it back together.

As far as I’m aware, this is the closest scientists have come to coaxing complex eukaryotic animal cells back to life after tens of thousands of years on ice. We have successfully revived viruses found dormant in the permafrost of thawing regions, but never managed to recover viable cells from a long-dead organism. To be clear, we still haven’t recovered viable cells today, and the researchers acknowledge that they haven’t cracked this problem yet.

To put the problem in computer terms: We took an ancient MFM hard drive, wired it into a modern PC, and observed that some of its mechanical components still functioned when appropriate commands were sent. We even ran a sort-of “chkdsk” on the drive itself, though this was unsuccessful within the context of the metaphor. What we haven’t managed to do is boot up an operating system or retrieve its contents. This is a significant step forward regardless, and a fascinating discovery.

Feature image courtesy of Wikipedia