Waking the Dead
We can, but should we?
There are Clones in our midst: on the street, in the supermarket, even in our homes. Nature calls them identical twins, and they occur when the first two cells of a fertilised egg, or zygote, unaccountably separate, instead of dividing into four cells as they do in the other 99.6 per cent of fertilisations.
Each of the twin cells goes its own way, developing into a separate individual. But because the two cells came from the same egg, the resulting progeny are genetically identical.
In the lab, we call that cloning.
You could clone an animal in your kitchen. Maybe not a Tyrannosaur, or even a Perendale, but life’s lower orders are a doddle to doppelgang. Hans Driesch cloned a sea urchin in 1885, simply by shaking apart two cells in an urchin embryo.
It wasn’t quite as easy cloning the world’s first mammal. Dolly, a Finn Dorset sheep derived from mammary gland cells (now you know why she was named Dolly), was born in 1996 to three mothers—one provided the egg, another the DNA and the third carried the cloned embryo to term. To make Dolly, Scottish scientists pioneered a technique that became the standard, known as Somatic Cell Nuclear Transfer (SCNT).
A somatic cell is any body cell that isn’t either a sperm cell or an egg cell. In mammals, every somatic cell has two complete sets of chromosomes, whereas sex cells, or gametes, only have one. In SCNT, geneticists remove the nucleus of a gamete, with its single set of chromosomes, and replace it with the nucleus from a somatic cell, which contains two. Because both sets of chromosomes come from the same donor somatic cell, the resulting embryo is genetically identical to it it (see graphic).
When such an embryo formed inside Dolly’s surrogate mother, it created cloning history. Dolly was the first product of a cell sourced from an adult mammal. The experiment also proved that genes implanted from a regular body cell could revert to an embryonic, pluripotent state—which is to say that they could develop into practically any tissue or organ with no loss of genetic material.
Since then, we’ve cloned deer, goats, horses and a gaur—a wild ox native to Southeast Asia. Around 30,000 gaur still survive in the wild, but hunting and habitat loss have driven the species to vulnerable status. In 2001, scientists at US biotech company Advanced Cell Technology (ACT) placed somatic gaur bull cells in the enucleated egg cells of domestic cows. The gaur nuclei directed normal fetal development—even as they were enmeshed in the cows’ mitochondrial DNA—to emerge as Noah, the world’s first clone of a threatened species, and the first to be derived from the eggs of a different species.
Noah was hailed as the way of the conservation future. With suitable genetic material, there was no reason an endangered species couldn’t be rescued by replication. But within 48 hours, Noah was dead, from dysentery. ACT staff insisted the bacterial infection was a commonplace hazard and in no way connected to its asexual ancestry.
Yet geneticists were already looking past threatened creatures, back into oblivion, to the burgeoning ranks of the disappeared. They dared to dream of resurrecting an extinct species. In 2008, scientists announced they had brought a tiny genetic piece of Tasmanian tiger back to life. The tiger became extinct in 1936, but when the researchers implanted some of its DNA into a mouse embryo, the DNA switched on in the nascent skeleton.
In 2009, hype around cloning ramped up when a French/Spanish team made the extinct Pyrenean ibex reappear—for seven minutes. The species had passed, somewhat ignominiously, when the last one, a female called Celia, was killed by a falling tree nine years earlier.
Celia’s well-preserved remains offered plenty of samples for cloning, but genetic fitness remains a problem. The 2009 clone died from respiratory failure shortly after birth. In previous attempts, only two embryos out of 54 survived the first two months of gestation before dying. (Dolly succumbed to pneumonia after just six years).
Besides, there’s a more fundamental problem; even if the team eventually rears a healthy Pyrenean ibex, there are no males left for any female clones to breed with. A solution would be to remove one of Celia’s X chromosomes and add a Y chromosome from another extant subspecies, creating a male Pyrenean ibex. Performing such an operation without irreparably damaging the cell will be tricky, but the technology exists, even if proven methodology doesn’t.
How far back into time could we go to wrest a creature from the cold grip of extinction? In November 2008, a Japanese team reported that it had successfully cloned from mice that had been frozen for 16 years. Inevitably, talk turned to woolly mammoths, carcasses of which have been emerging, courtesy of climate change, from the thawing ice caps in increasing numbers.
But freezing DNA doesn’t automatically preserve it. Over the 10,000 years since the mammoth disappeared, the material has still degraded, leaving gaps in the genome you’d need to fill before you could produce a healthy animal. We’re getting close with the mammoth; using African and Indian elephants as a template, a US team has sequenced some 70 per cent of the creature’s estimated 4.5 million base-pair genome, prompting talk of synthesising the rest of it.
It won’t be easy; the mammoth’s code differs from that of today’s elephants at about 400,000 sites. Each chromosome would have to be laboriously re-engineered from modern material.
Even if that could be done, the entire genome would need re-sequencing to weed out any errors introduced by time and degradation, then it would all have to be ordered into chromosomes. Yet it seems do-able; new high-speed sequencers and better methods of DNA extraction have turned cloning more into a question of money.
And ethics. The mammoth project represents an enormous expenditure to re-create what would essentially be an exhibit. And is it fair to create an animal doomed to captivity and loneliness?
Nearly half the original cast of our own Jurassic Park has vanished, lost to the spear, the axe and the teeth and claws of introduced pests. The lure of again watching the shadow of a Haast’s eagle darken the forest is seductive, but would cloning a huia, or a piopio, or a moa—raising them from the dead—simply be a salve for our troubled conscience?
For now, we’re spared such hefty moral conundrums—their delicate egg cell structure makes birds poor candidates for SCNT. However it makes unshakeable sense to bank the DNA of our most critically-endangered species—the fairy tern, the black stilt, the kakapo, the black robin—as a hedge fund against some catastrophic disease or disaster that would otherwise wipe these relict populations off the planet. The Frozen Ark in the United Kingdom is just such a facility, set up as a conservation vault where the ingredients of our biodiversity are kept in liquid nitrogen at minus 195ºC.
The most valuable role for cloning may yet lie in helping to slow the rate of extinctions, rather than trying to reverse them. But in all these endeavours we could do worse than heed the oath required of all doctors:
Most especially, must I tread with care in matters of life and death. If it is given to me to save a life, all thanks. But it may also be within my power to take a life; this awesome responsibility must be faced with great humbleness and awareness of my own frailty. Above all, I must not play at God.