Sunday, 22 February 2015

Extinct species/subspecies that could be revived through cloning


Cloning probably is the only possible way to revive an extinct species or subspecies. But people inevitably associate it with Jurassic Park, Dolly, and clueless priests that delight us with their dispensable comments. Also, people always raise the following questions:

Can we do it? (I am not a geneticist, but see below).

Should we do it, what good is in it? I hate this question. It is exactly that kind of ugly pragmatism that is the death of science. Why studying anything that doesn’t bring mankind any immediate advantages? We research for knowledge’s sake. Apart from that, it can have a practical good since most species exterminated by man were part of modern ecosystems. People often argue that cloning a single individual would be pointless because you cannot recover a whole species from it and the animal would suffer from its aloneness. First of all, what if we find the absolutely last moa in the NZ forests? Would we preserve and study it, or would be roast and eat it? A cloned woolly mammoth would be the only member of its species just in the same way. Apart from that, many species that can be socialized with animals of other species if there are no conspecifics in captivity, such as African and Asian elephants (why not mammoths?), and some of the cloning candidates might have been solitary anyway (the Thylacine, for example).

Is it ethically correct? Yes it is. At first, why should it be a problem to restore something that previously has been destroyed by man? And even if it is a species that did not die off because of us, I still see no problem. “Playing evolution?” We always did, we always do, we are a part of evolution. And nobody is planning to release an alien extinct species into an ecosystem where it does not belong. Of course there are people who have ethical problems with cloning in general, but animals get cloned every day for non-scientific reasons, so annoy the people who do that instead those who do it for scientific reasons.

Is it dangerous? This is the most ridiculous question. What do those people think, that Woolly mammoth get cloned, released somewhere without a reason, thrive and reproduce like rats and destroy whole ecosystems? And no, cloning extinct animals does not recreate ancient pathogens that cause ecologic and humanitarian catastrophes and so on. And if you think cloning extinct animals is dangerous because the animals themselves are dangerous, stop watching JP and grow a brain.   

The “argument” that perplexes me the most is why we should try and invest in it if we do not know if it is going to work in the end. What kind of whacked moral is that? If we would only try of which we know it is going to work we would still live in the Palaeolithic. It is the task of science to find out if something is going to work or not.



Is it possible at all?



I am not a geneticist, but everybody will agree that it won’t be easy. The first challenge is to recover enough intact nuclear DNA. Then, as far as I understand, a complete set of functional chromosomes has to be created, because merely a known base sequence is not sufficient to clone an animal. And this step is not possible yet, but scientists are working on it. After that, the genetic material has to be implanted into a blastocyst and a suitable surrogate has to be found that is compatible in immunological, epistatic(?) and morphological way. And not to forget, you need both types of gonosomes. Considering all that, the number of species having a chance of revival gets drastically reduced. A clone only shares the nuclear genome with its original while it has the mitochondria of its surrogate. However, mitochondria only have a few number of genes and most of them are for the organelle itself, so this should have virtually no impact. I do not know how much the influence of epigenetics would be, but probably not that large either (correct me if I’m wrong).



And there is a difference between cloning one or a few individuals and the recovery of a viable population. In most cases, probably only a few individuals or perhaps only one could be cloned, which is of course not quite a good basis. But some of those species have close and similar relatives that can contribute additional genetic material. Pedigree fanatics would claim that the result would not be a “pure” population anymore, but the gene pool of species always changes. Even if the number of cloned individuals is large enough for a whole population, its gene pool would still differ from those the individuals originally are from due to genetic drift, which is natural and omnipresent. Apart from that, many species experience hybridization in the wild anyway. Note that I am not suggesting lez a faire hybridization, but careful absorptive breeding. That is, for example, supplement the group of cloned Quaggas with some Plains zebras, but only mares (unless no Y chromosome of the species in question has been recovered; or the female Z chromosome in the case of birds). Remove the hybrid stallions in the first generations. Later on, when the population is allowed to breed freely, remove those individuals that might show some features of the “diversity donors”, be it optic, behavioural or whatever.





What kind of sources?



There are numerous sources of organic material that can be used to gain genetic material. Leukocytes, hair, feathers, most types of soft tissue and even bone. It is said that DNA has a maximum life span of 500.000 years, so the number of species is limited. Mummified specimens can contain DNA, so do well-preserved bones, which is what we find at good permafrost and other late Pleistocene and early Holocene sites. Another source are specimen preserved in alcohol. It has been tried to gain functional DNA from conserved Thylacine embryos. Also preserved skins may contain DNA, as it has been successfully extracted from Thylacine skins in 2009. Imagine of how many extinct species DNA might still be present because there are preserved skins!

The fact that the whole genome of an aurochs based on an early Holocene skeletal remain opens an interesting possibility: genetic material of far more late Pleistocene and early Holocene species could be recovered. Perhaps a few Wisent individuals could be completely resolved and cloned, which would be a great leap towards overcoming the inbreeding depression of this bovine. As if this wouldn’t be awesome enough, perhaps there is enough preserved DNA of late Pleistocene species of which we have numerous, well-preserved skeletal remains to clone a number of them – say hello to woolly rhinos, direwolves, Mammuthus columbi, perhaps even sabre-tooths. Ground sloths probably not, because there are no suitable surrogates. But this is just imaginary anyway (yet).



The species



What I do now is to present a list of species that are candidates for a revival through cloning. Some of them are more likely than others, and some of them have already been proposed, others not.

Alphabetical order:



Aurochs

In 2013 it has been reported that the whole genome of an early Holocene bull aurochs has been resolved thanks to well-preserved bone remains. Perhaps it is possible also to resolve the complete genome of more individuals. If it is possible to recover the nDNA of five different aurochs from different locations and ages, it might be a more diverse pool than that of the wisent already. And, not to forget, there are many suitable breeds to add genetic diversity with minor influence on appearance and nil in all the other respects. There is an enigmatic Polish group called PFOT that allegedly wants to genetically reconstruct the aurochs.



Bluebuck

Killed off in 1799 or 1800, only four mounted skins and few bone and horn material left. Therefore there is not much material to go on, but surrogates would be no problem. This species has not been suggested for cloning yet.



Dodo

No skins, skeletal material suboptimal. There is only one specimen with remaining soft tissue, the Oxford specimen, which consists of a foot and head rescued from destruction. DNA was taken from the leg. I am an optimist and hope that it might be possible to obtain a complete genome. But probably there is no suitable surrogate, as all living pigeons are way too small and all birds of suitable size are only very distantly related to the dodo. The dodo as a candidate is just a rampant idea of mine.



Gastric brooding frog

In 2013, a living embryo of this amphibian was created with somatic nuclear cell transfer. The embryo failed to turn into a tadpole, but scientists are confident to create living gastric brooding frogs, which disappeared in the late 1980s. So achieving a single member of this species is very likely about to come, but I don’t know if there is enough material for a whole bunch of individuals.



Great auk

There are about 80 (!) skins of the Great auk, so the chance to get enough material for several individuals or at least one, is high in my opinion. Hopefully, the razorbill, the closest living relative of the Great auk, is a suitable surrogate. If someone seriously tries and enough DNA is recovered, I do really see a good chance for not only one but a breeding group of great auks to be created. This species has not been suggested as a cloning candidate yet.



Kouprey

It is not sure whether or not the Kouprey is extinct or not. No individual was spotted after the 1980s, but on the other hand nobody has made a serious attempt to find one. For this article, let’s assume they are extinct. I don’t know the exact number, but there are a few skins, plus numerous trophies, mostly skulls with horn sheaths. Surrogates would be no problem (domestic cattle), and there would be species that could serve as “diversity donors” (Banteng and Gaur). The Kouprey has not been suggested either, perhaps people should try to find remaining living ones first. Cloning “additional” Koupreys would help to increase the genetic diversity of this species if it still exists, as I suggested for the wisent.



Passenger pigeon

There are a lot of stuffed passenger pigeons and they would have suitable surrogates, so the chance to clone a few individuals is not bad. Problems for breeding are that they stopped breeding after their population dropped below a certain number. But: theoretically, if a large number of clones is produced they might indeed breed if the number is large enough. The pigeons wouldn’t know that some of them are clones of one and the same animal. However, that would be pretty effortful I think.

I don’t know if there are people that consider truly cloning a passenger pigeon, but there is that project that tries to identify single genes responsible for typical phenotypic traits of this species and wants to insert them in living pigeons. Not sure what to think of that.



Pyrenean ibex

The Pyrenean ibex, also called Bucardo, in fact had been cloned already and was the first cloning attempt of an extinct animal. Over 200 embryos were produced, but eventually only one was born alive. For about seven minutes, the bucardo was alive again, but died afterwards because of a defect of the lungs. This is a general problem of cloning with adult somatic cells, and not because it was a transspecies clone. One female is certainly not enough for a population, but perhaps there are enough skins and skeletons to recover a complete set of DNA from a number of individuals.



Quagga

There are more than twenty Quagga skins on display, all of which could house nuclear DNA. Furthermore there are two mounted skeletons on display and I assume that surely large quantity of material is in collections, maybe also as trophies. If one or a number of Quagga can be cloned, the herd could be supplemented with plains zebras, preferably from the Quagga Project, to gain more genetic diversity. Unfortunately the quagga was not considered for cloning yet, as far as I know.  



Thylacine

This is, next to the Woolly mammoth, possibly the most famous candidate for cloning. A project started in 2000 using an embryo conserved in alcohol was stopped in 2005 because the DNA turned out to be too damaged. 2008 a gene involved in cartilage formation extracted from a Thylacine was inserted into a transgene mouse and did its function perfectly. The Thylacine Sequencing Project currently tries to resolve the complete genome of the Tasmanian tiger. They themselves do not believe in a resurrection of the Thylacine in the near future. One of the problems is the lack of a closely related surrogate (the Tasmanian devil has been suggested previously).



Upland moa

A moa is an “optimistic” idea of mine. There are numerous well-preserved skeletons of all moa species, but I choose the Upland moa because there is one mummified specimen of it and it is probably not too large to be carried out by an Ostrich or Emu. The challenge is to recover enough genetic material and if living ratites can serve as surrogates at all, because they are only distantly related. Nobody considered cloning a moa yet, and I don’t know if there are even efforts to fully resolve the genome of one of the 12 species.



Western wild horse

This is “just an idea” as well. If it was possible to reconstruct the full genome of an aurochs based on bone material from the early Holocene of Europe, it might be possible with remains from European wild horses as well. Skeletal material of domestic and wild horses are difficult to distinguish, but genetics will show. If indeed a few wild Equus ferus ferus can be cloned, and if the diversity is not large enough for a viable population, they could be supplemented with primitive horse breeds, depending on which resembles them closest.



Woolly Mammoth

Three ways have been proposed to resurrect the Woolly Mammoth. The first is classical cloning, for which a complete genome is needed. As far as I know, 70% of the nuclear genome of the Woolly Mammoth are resolved yet, but scientists are working on it. The second one is to recover intact sperm cells and inseminate an Asiatic elephant cow, and to breed an almost fullblood Mammoth by absorptive breeding. However, it sounds really implausible to me that such well-preserved sperm cells can be found in a frozen carcass that is at least 10.000 years old. The third method is to take the chromosome set of a living elephant and to track down the loci that differ in the two species, and to exchange the elephant alleles with the mammoth alleles to create a set of chromosomes that can be used for cloning. The mammoth DNA would have be known completely, otherwise the result would, technically, be a hybrid, as far as I understand.



Steppe bison

There are hundreds of well-preserved Steppe bison remains in turf and permafrost, some of them mummified. So there might be the chance to acquire full genome, perhaps of more than one individual. Surrogates are no problem – wisent and American bison. Both species would also be prime “diversity donors” if there is not enough diversity for a whole population.

Coelodonta might be another candidate for recovering a full genome from these kind of sources.

Nobody suggested these species for cloning yet, and I don’t know if there are efforts for resolving their full nuclear genome.



This list might fill us with hope that we might see a lot of extinct species back again. However, I think it is optimistic already if we expect this to happen in more than one or two species. Not only because of the technical challenges, but also because there is little scientific interest and little founding, because people don’t see “the good” in it, or why we “should” do it, and there are always those unjustified worries and “ethical” nonissues listed above. It is frustrating.


4 comments:

  1. Great post! I am very frustrated as well. It's hard for me to understand why so many people are against doing everything they can to bring some of these amazing animals back into the world.

    Also, I think you would be interested in the Long Now Foundation's "Revive & Restore" initiative. They are looking to group together people who are trying to bring some of these animals back. Several of the species you mention in this post are also candidates on their list.

    http://longnow.org/revive/candidates/

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  2. There is optimism that a recently found Coelodonta mummy could preserve DNA.

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    1. I've heard of that recently found mummy, but I know nothing more about it. Do you have some info, maybe?

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  3. northern white rhino would be my first choice followed by the various extinct tiger subspecies.

    amongst birds; carolina parakeet seems like it should be doable eventually - there must be lots of skins.

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