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Back from the dead

JURASSIC PARK will always remain in the realms of science fiction. But the
question of whether scientists have ever managed to extract any genetic material
at all from ancient fossils is far more controversial.

According to Richard Thomas and his colleagues at London’s Natural History
Museum, writing in the August issue of Trends in Ecology and Evolution:
“It is highly unlikely that geologically ancient DNA survives in any fossil
material so far studied.” The researchers spent three years attempting to
extract DNA from insects entombed in amber. “We worked with many more samples
than the total number of published reports of success,” says Thomas. The result:
complete failure. Not a single strand of prehistoric DNA to be seen.

It looked as though the field of ancient DNA research, which in its short
life had travelled like a roller coaster between expectation and disappointment,
had reached the end of the tracks. But then came newspaper headlines proclaiming
that scientists had successfully extracted DNA from the fossilised bones of a
Neanderthal individual who had lived as long as 100 000 years ago
(This Week, 19 July, p 5).

Questionable claims

How can the conflicting findings from a decade and a half of ancient DNA
research be reconciled? “The original studies look like bad science, I’m
afraid,” admits Rob DeSalle of the American Museum of Natural History in New
York, and coauthor of a claim for the recovery of DNA from a termite trapped in
20-million-year-old amber. “We have to deal with this now.” But the
Neanderthal DNA results, which were replicated by independent scientists, do
stand up to scrutiny. “That is very sound work, and I’m sure their claim is
valid,” says Thomas. The bottom line, however, is that DNA is highly unlikely to
survive longer than a few tens of thousands of years, and even then only under
extraordinary conditions of preservation such as a cold, oxygen-free and
waterless environment.

When an organism dies, its tissues immediately begin to break down, creating
a soup of enzymes, water and oxidative molecules that cut DNA strands into
smaller and smaller fragments. As time passes, the amount of DNA remaining in
the tissue steadily diminishes, and eventually disappears entirely. Ancient DNA
research, therefore, hinges on the ability to extract vanishingly small
quantities of DNA from such tissue and to amplify this genetic material to
produce enough to work with. This DNA amplification technique, known as the
polymerase chain reaction (PCR), was developed in 1985. Within five years,
previously unthinkable claims were being made.

The first, in 1985, was that scientists had extracted human DNA from an
Egyptian mummy almost 2500 years old. Then researchers claimed they had
recovered DNA from a specimen of the extinct ground sloth, some 13 000 years
old, and a woolly mammoth that had been trapped in the Siberian permafrost
around 40 000 years ago. But the most dramatic reports began early in 1990, when
researchers at the University of California, Riverside, announced the recovery
of DNA fragments from 17-million-year-old magnolia leaves, from a deposit in
Idaho. This was followed in 1992 and 1993 by truly mind-boggling reports of
multimillion-year-old DNA from specimens entombed in amber: a termite (25
million years old), a bee (40 million) and a weevil (130 million). The
glamorisation of this field of research was completed in the mid-1990s, with
reports of DNA extracted from an 80-million-year-old dinosaur bone, and claims
for the resurrection of dormant bacteria and fungi extracted from insects in
40-million-year-old amber.

However, two dark clouds appeared on the horizon. First, DNA simply should
not survive outside living systems for a million years, let alone tens of
millions. The claims “don’t make any sense”, wrote Tomas Lindahl, a pioneer in
DNA chemistry at the Imperial Cancer Research Fund, in 1993. Secondly, PCR is so
powerful that any tiny fraction of DNA present in the sample—whether
ancient or modern—may be extracted and amplified. Researchers began to
realise that contamination was a major problem.

Handle with care

The challenge of reliably extracting DNA from ancient material is illustrated
by the immense amount of painstaking work that was involved in retrieving
Neanderthal DNA, which Lindahl describes as “a landmark discovery” and “the
greatest achievement so far in the field of ancient DNA research”. The project,
led by Svante Pääbo of the University of Munich, was successful not so
much through novel technology as through extreme care, the use of multiple
controls, and enlisting a second laboratory to replicate the work.

But even if other teams were able to mount such an effort, it might not be
worth it, says Thomas. Many valuable specimens would be destroyed in the search
for the few that contain DNA.

Thomas and his colleagues Jeremy Austin and Andrew Smith believe that their
recent work implies that most, if not all, of the DNA extracted from insects in
amber and other ancient fossils is a contaminant. The putative dinosaur DNA, for
instance, almost certainly came from human contamination. “The Natural History
Museum’s work is very good, very carefully done,” concedes DeSalle, whose claim
of 20-million-year-old termite DNA it explicitly questions. “I looked at our
data again, but I can find no other way of explaining them than as we did
before,” he adds. “I’m perplexed that they didn’t succeed.” Nevertheless,
DeSalle agrees with Thomas’s team that rare samples of insects in amber should
not be sacrificed in the search for headline-catching results, because the
chances of success are low, and the current techniques are too prone to
contamination.

Most researchers accept this message, but reactions to the team’s gloomy
conclusions are mixed. At one end of the scale are those experts who, like
Michael Braun of the Smithsonian Museum’s laboratory of molecular systematics,
believe “it’s the end of the story for very ancient DNA”. At the other are
authors of the original reports, who defend their work. For instance Edward
Golenberg, who reported the ancient DNA from 17-million-year-old magnolia
leaves, warns against “extrapolating too far from negative results”. “The death
of ancient DNA research has been overstated,” he says.

Raúl Cano of California Polytechnic State University, author of some
of the more spectacular claims for ancient DNA extraction, including
resurrecting long-dead microorganisms, is equally combative. “Just because they
failed doesn’t mean that we did,” he says. “They are too dogmatic in their
conclusions.” It is worth noting, however, that other research teams have tried
and failed to replicate the amber claims. These include investigations by
Pääbo, a pioneer in ancient DNA research and its most respected
practitioner. “The burden of proof is now on those that claim it can be done,”
he says.

So does ancient DNA research have a future? Thomas believes so. “It is simply
taking on a different focus,” he says. The world’s museums are full of animal
and plant specimens that could provide a source of DNA for investigating
evolutionary changes during the past few hundred or few thousand years. “This is
important work, even if it doesn’t have the glamour of Jurassic Park.”

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