Nov 06 2008

Cloning the Frozen

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Researchers from Kobe, Japan have successfully cloned a mouse using the DNA from a mouse that had been frozen for 16 years. This is an interesting incremental advance in cloning technology. Using DNA from a previously frozen specimen has been done before, but using a specimen frozen for about 3 years. This significantly increases the time frozen to 16 years.

Cloning (specifically reproductive cloning) is the technology of taking the nucleus of one cell and placing it into an egg whose own DNA has been removed. The egg then needs to be stimulated, either electrically or chemically, to trigger the process of division and development. The result is an organism that is a twin (sort of) of the individual from which the donor DNA was taken. The resulting clone is actually less identical to the donor than twins are to each other. Twins also share the same parent egg (not just nuclear DNA – for example, there is also mitochondrial DNA outside the nucleus), and the environment of the womb.

There are two other types of cloning. Recombinant cloning places pieces of DNA into a host cell so that it will become incorporated into it. This has been done for decade, to make bacteria, for example, that will produce drugs or other useful chemicals. There is also therapeutic cloning, a topic of some controversy, whereby eggs are created not for the purpose of developing into a living creature, but to provide raw material for research or potential therapeutic applications.

This current research deals with reproductive cloning. It is of extreme interest how long DNA can survive in a frozen state before it degenerates beyond usefulness. This is because of the very cool prospect of resurrecting the woolly mammoth and other ice-age mammals. (Side note – I see “whooly”, “wooly”, and “woolly” in roughly equal proportion, but the most authoritative sites seems to prefer “woolly”.)

My favorite is the woolly rhinocereos. Take a look at the photo here – this is a story of a little girl who found a woolly rhino fossil at the park.

Occasionally ice-age mammals are found frozen in the permafrost – which means they have been frozen since death. Soft tissues are preserved. The most common species to be found is the bison, but rarely mammoths have been recovered.

This raises the intriguing possibility of cloning a mammoth and returning, for the first time, a species back from extinction. Mammoths are closely related to living elephants, so they would make perfect surrogate. There are a couple of approaches that have been proposed. The first is to simply clone a mammoth – take a nucleus from a frozen specimen and implant it into an enucleated elephant egg. The result would be a full mammoth. If we can make even a few clones in this way, then it is theoretically possible to nurture back into existence a self-sustaining population.

Another approach is to recover the frozen sperm or egg from a mammoth and then use that to fertilize an elephant egg. This is much easier and more likely to work, but the result would be half elephant and half mammoth. However, this process can be repeated several times with the half-breed offspring, each time fertilizing the partial mammoth with full mammoth sperm or egg. After a few generations the result would be mostly mammoth.

The problem with both these approaches is that DNA does not survive unscathed for thousands of years. While 16 years is a nice proof of concept, it is not 10,000 years. Also, the mouse was preserved for 16 years at a constant temperature (-20C) in the lab. This is different than the fluctuating temperatures out in the wild. And, while freezing temperatures in the arctic are cold, they are not cold enough to prevent decay – only to slow it.

Still, we can recover some (albeit degraded) DNA form frozen mammoths. Perhaps we can sequence the mammoth genome. Computers could analyze thousands of fragments and assemble them, like a puzzle, into an intact genome. We could then compare this to the genome of a living elephant – then we would only need to tweak the sequence to change an elephant into a mammoth.

This project is already under way. Hendrik Poinar of the McMaster Ancient DNA Centre at McMaster University in Hamilton, Ontario has been sequencing the mammoth genome. He has already sequenced a number of nuclear genes. They have found that the mammoth genome is 98.55% identical to the African elephant. This is consistent with the fossil evidence suggesting they split about 5 million year ago.

Apparently this project is slowed due to lack of funding, which would be a shame. Genetic information is information – once lost it is lost forever. The paleogenomics project is an attempt to gather this information and reconstruct it before it is lost.

Similar efforts are also underway for recently extinct species, like the thylacine (Tasmanian tiger).

There are several important aspects of this kind of research. There is no doubt that human activity is wreaking a mass extinction on this planet. While we need to explore way to minimize this, developing the technology to preserve the genomes of lost species is an important hedge against man-made extinction.

Second – how totally cool would it be to go to the zoo and see a woolly rhino or mammoth? It would be like a trip back in time. This coolness factor is potentially important – cool science that sparks the imagination is important to getting children interested in science, and to continue public support (i.e. funding) of science.

Resurrecting the woolly mammoth, if played properly, could inspire a generation of biologists and geneticists the way the moon landings inspired a generation of engineers and astronomers.

I am not saying science is only important when it is dramatic and entertaining. But when we have such science that is accessible to the public, it is an opportunity that should not be missed.

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