No dinos or dodos will be resurrected

May 30, 2003

The study of ancient DNA is fascinating enough that it needs no flights of fancy, says Alan Cooper, the head of Oxford's new centre devoted to the subject. Claire Sanders reports.

When it comes to ancient DNA, the temptation to sensationalise is almost overwhelming. Could we have dodos for pets? Could we re-create Neanderthal man? Would dinosaur-theme parks really be such a bad idea?

For 37-year-old Alan Cooper, director of the new Henry Wellcome Ancient Biomolecules Centre at Oxford, the study of ancient DNA is sufficiently fascinating to do without such flights of fancy. "Much of my career has been spent putting out fires and establishing standards. We need to get away from fanciful stories to a more thorough understanding of the detailed detective work involved," Cooper says. "This is why we have set up the new centre at Oxford."

Speaking in a small office next to the construction site that will soon be one of the centre's two buildings, Cooper repeatedly refers to himself as a detective, painstakingly seeking the truth.

His career in DNA detection began in the caves of his native New Zealand.

"Between the ages of 15 and 23, I spent all my spare time underground, and I specialised in digging out rockfalls to get to concealed passages. A common digging tool was the bones of the moa," he says. The moa, a giant New Zealand bird that could be up to 3m tall, died out about 400 years ago.

In 2001, after completing a PhD at the Victoria University of Wellington and working at the Molecular Genetics Laboratory at the Smithsonian Institution, Cooper moved to Oxford to study Neanderthal DNA.

He also continued his interest in the moa, although now showing his old friend a bit more respect. His team was the first to sequence the entire genome of mitochondrial DNA of an extinct animal.

Mitochondria are the energy-producing structures within cells, and their DNA account for less than 1 per cent of an organisms's complete genome, with the remaining genes found on chromosomes in the cell nucleus.

A year later, the centre also retrieved small fragments of mitochondrial DNA from the extinct dodo, using the 300-year-old "Alice in Wonderland" specimen - so called because it was the inspiration for the character in the Lewis Carroll book.

The retrieval of mitochondrial DNA of these flightless birds cast new light on their nearest living relatives and on the evolution of other flightless birds. But the work also cast light on just how difficult it would be to re-create extinct creatures from ancient DNA.

Cooper's view is that such an exercise is basically impossible - and not worth the effort. The problem is that ancient DNA is so badly degraded that it is impossible to determine the original sequence through long regions of junk, or repetitive, DNA. "The mitochondrial genome is only 17,000 base pairs long, and it is just a tiny part of the roughly 3 billion base pairs in the complete genetic code of a bird," he says. "Although we can sequence the small pieces of surviving ancient DNA, we can't stitch them together in regions where the sequence is just random-looking junk. Even just sequencing the small mitochondrial genome brought that fact home very quickly."

But if research into ancient DNA can't bring back the dodo, what can it do? Projects under way include large-scale studies of the effects of global climate change on animal and plant populations through time, the evolution of bacterial and viral pathogens and the study of human evolution and migration.

Crucially, because the projects take a cautious forensic approach, they are overturning old assumptions. Tom Gilbert, a researcher at the centre, has found that ancient DNA can trick researchers as it degrades.

"We have been looking at DNA from Viking and other human remains, and we found that post-mortem damage is not randomly distributed along the DNA molecule," he says. "Instead, the degradation is concentrated at certain nucleotide hot spots that appear to be predisposed to attack. Many of these hot spots have also been observed to mutate at elevated rates in living humans. In the case of several of the Vikings' DNA, the damage occurred at a certain spot that population geneticists use to distinguish European DNA sequences from those more commonly found in the Middle East. As a result, the Viking skeletons appeared to be from the Levant."

Cooper says: "Strangely enough, we can now use the patterns of damage caused after death to examine how DNA damage actually occurs during life - a completely unanticipated and somewhat ironic result."

The accuracy of such research will increasingly rely not only on careful procedures but also on state-of-the art facilities. The centre's £1.4 million building has been funded through the Joint Infrastructure Fund.

When it opens, its only equals will be the US Armed Forces Institute of Pathology in Washington DC and the Max Planck Institute in Germany.

The facility will be isolated from others because modern human DNA can so easily contaminate ancient DNA. Researchers will wear protective clothing and will not be allowed into the ancient facility if, on the same day, they have been into a building where molecular biology is conducted. "This system relies on researchers going home at nights and having showers and baths," says Cooper - who points out that we are talking about postgraduates rather than undergraduates.

"The amount of DNA preserved in old specimens is vanishingly small and can be contaminated by human skin flakes and even exhaled cells," he says. "The risk of contamination is enormously magnified in modern biology buildings, where research often involves the amplification of DNA to huge concentrations, making trillions of copies."

Laboratories will have filtered air supply systems to isolate the researcher and all equipment, and supplies entering the ancient centre will pass through an ultraviolet sterilisation system.

"This purpose-built environment will create one of the first ancient DNA research facilities with essentially zero levels of background DNA, permitting large-scale studies of extinct and prehistoric animals, plants and pathogens," Cooper says.

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