7 octobre 2016

Cloner des espèces éteintes?

Cela pourrait se produire plus tôt que vous le pensez:

(...) On a midsummer’s day in 2003, a group of Spanish and French scientists helped a goat bring a 4.5 pound kid into the world. Normally, a goat birth wouldn’t be worth noting in the history books, but Celia was no ordinary baby goat. In fact, she wasn’t a baby goat at all. She was a Pyrenean ibex, and her kind had gone extinct three years earlier.

Ten minutes after her birth, Celia died, and the Pyrenean ibex was pronounced extinct once more. A necropsy revealed the cause of death: There was an extra lobe in Celia’s lungs, and it was solid all the way through.

Celia’s time in the world was brief, but to the scientific community, the significance of her birth can’t be overstated. With Celia’s birth, the notion of de-extincting life was no longer a pipe dream—suddenly, it seemed very much within reach.

In many ways, the Pyrenean ibex was a natural de-extinction guinea pig. Hunters had driven the large, mountain goat-like animal to its demise a mere decade earlier, and when the last wild individual (also named Celia) died, samples of her tissue were preserved frozen in laboratories. All scientists had to do was transfer the DNA contained within Celia Sr.’s cells into goat eggs emptied of their own genetic material, implant the chimera eggs into a surrogate mom, and hope one would grow and come to term.

They tried over 400 times. Celia Jr.’s ten minute life was the furthest they got.

Halfway across the world, a group of Australian researchers who call themselves The Lazarus Project are now using similar methods to try and restore two other casualties of the human race: Rheobatrachus vitellinus and Rheobatrachus silus, the northern and southern gastric brooding frogs. First discovered in the 1970s, these two species of frogs inhabited tiny patches of pristine rainforest in eastern Australia. But by the early 1980s, both species had vanished, probably due to habitat loss and the introduction of a pathogenic fungus.

During our brief time studying them, scientists learned that gastric brooding frogs have a fascinating reproductive cycle. After her eggs are externally fertilized, the female gastric brooding frog will swallow her embryos whole. A hormone in the eggs triggers the mother to shut off stomach acid production, effectively turning her gut into a womb. After a few weeks of gestation, she regurgitates a slew of tadpoles. The disappearance of this unique mode of reproduction was a major loss to the scientific community — and to natural diversity.

That’s why the Lazarus crew, led by University of New South Wales professor Michael Archer, have spent the last six years trying to bring the frogs back. Similar to the earlier (and cruder) Pyrenean ibex de-extinction effort, Lazarus scientists are attempting somatic nuclear transfer, sucking the nuclei out of gastric brooding frog cells and transferring the genetic material into the live eggs of distantly related barred frogs. The work is slow going, as frog eggs lose their potency after a few hours and can’t be revived. And because of the barred frog reproductive cycle, the scientists effectively have a single week every year to make a real go of it.

In 2013, the Lazarus team announced that they had successfully grown embryos containing DNA of the extinct frogs. But so far, none of the embryos have developed properly. As the Sydney Morning Herald recently reported, Lazarus scientists are finding traces of the host frog’s DNA in embryos where it should have been removed. Archer suspects these two sets of genetic instructions are confusing the embryos and holding back development. Still, the fact that gastric brooding frog DNA is replicating at all inside host eggs is exciting progress, and the Lazarus team isn’t giving up.

Our attempts to bring back the Pyrenean ibex and gastric brooding frog highlight the enormous technical challenges of cloning and reviving lost organisms. And yet, both efforts have focused on a very recently extinct animal, and have been blessed with cryopreserved cells containing high-quality copies of the organism’s DNA.

(...) But for creatures that disappeared hundreds or thousands of years ago, finding a perfectly preserved copy of the animal’s genome is nigh impossible. After death, DNA begins to decompose and degrade almost immediately. Even if an creature freezes shortly after dying—one could imagine, for instance, a mammoth in the Siberian permafrost—its DNA will, over time, crack and splinter. (A recent study predicts that even at the ideal preservation temperature of -5ºC, every bond in a DNA molecule would effectively be destroyed after 6.8 million years, setting a firm upper limit on the ancient organisms we can hope to revive).

Inevitably, paleogeneticists are left with the onerous task of reconstructing the extinct creature’s entire genetic library from fragments, which is essentially analogous to piecing together a book from a copy that went through a paper shredder. How do we even begin to do so?

To find out, I spoke with Ben Novak, a paleogeneticist at Revive and Restore who is currently leading up the effort to de-extinct the passenger pigeon, a famous North American bird whose populations numbered in the billions before humans shot them all from the sky in the 19th century. As a first step, Novak and his colleagues have spent the last few years reconstructing the extinct bird’s genome. Since we don’t have any frozen specimens at all, scientists have had to rely on tissue samples from taxidermy animals housed in museums.

“Passenger pigeon DNA is really fragmented,” Novak told me. “The pieces we get are anywhere from 30 to 150 base pairs in size.” To give you an idea of what this means, a base pair represents a single letter in the DNA code. The entire passenger pigeon genome contains 1.3 billion of them.

“We don’t get anything big, and it’s very, very difficult to piece any of that together, because not only is it short, it’s riddled with false mutations from damage,” he added.

And yet, the speed and accuracy of our DNA sequencing technology has advanced to the point where we’re able to take the many reads needed to spit out all the sentence fragments in a broken genome. But to put the pieces back together, scientists need a reference genome—a very similar book that’ll serve as a guide. This past March, Novak and his team completed genomic sequencing for the band-tailed pigeon, a close living relative of the passenger pigeon that differs in roughly 3 percent of its DNA. Using the band-tailed pigeon as a map, they’ve successfully reassembled several complete passenger pigeon genomes.

Getting the passenger pigeon’s genetic code written and pieced together was an enormous achievement, but still, it’s only the first step toward a much larger goal. To find out what parts of the genome encode for meaningful passenger pigeon traits, the team’s next goal will be to look at RNA—transcript copies of genes that cells use to make proteins. Once they’ve sequenced the band-tailed pigeon’s entire RNA library, or transcriptome, they can use to the information to identify important genes within the passenger pigeon genome.

“That’s when we start doing the fun preparations for trying to make a bird,” Novak told me.

Unlike the Pyrenean ibex or gastric brooding frog, scientists aren’t going to be able to stick the entire passenger pigeon genome inside a host egg. Bird eggs are enormous, not to mention that they’re enclosed in a hard outer shell. Novak compares removing the tiny, DNA-containing nucleus from a bird’s egg to finding a white marble in a vat of milk. And inserting a new nucleus containing other genetic information is another can of worms entirely.

Instead, the current plan is to use CRISPR gene-splicing technology to cut out pieces of band-tailed pigeon DNA from germ cells and hack in the corresponding passenger pigeon traits. In this manner, scientists can create hybrid cells containing all the important genes that distinguish the passenger pigeon from its close cousin. Hybrid cells cooked up in petri dishes will then be injected into the bloodstream of developing band-tailed pigeon embryos, where they’ll eventually migrate to the gonads. After the eggs hatch and the squabs mature, some of their eggs or sperm will contain the instructions for an animal that looks a lot like a passenger pigeon. Another generation of captive breeding, and a small number of passenger pigeon-like individuals could be born.

Nothing like this has ever been done before, and nobody’s quite sure how it’ll all go down. But the passenger pigeon isn’t the only animal we’re trying to hack back into existence one gene at a time.

Similar efforts to revive the wooly mammoth are moving full steam ahead. In April, a team of researchers at McMaster University’s Ancient DNA Center published the most complete wooly mammoth genomes to date representing two individuals whose remains were buried in the Siberian tundra 40,000 years apart. Meanwhile, Harvard geneticist George Church and his colleagues are busy using CRISPR to splice genes for mammoth ears, subcutaneous fat, hair length and color into the DNA of elephant skin cells. These chimera cells, while a far cry from a bonafide mammoth, show that the dream of recreating the iconic Pleistocene elephant is very much alive and kicking.

(...) More saliently to the Jurassic Park-loving public, the idea of de-extincting life inspires wonder and awe. We may never see live herds of brachiosaurus stampede across a tropical island, but the technology to reproduce a 40 thousand-year-old Pleistocene mammoth is now within reach.

I don’t know about you, but I think a herd of mammoths stamping across snowy northern Canada would be a pretty cool thing to see.

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