Neanderthal Man: In Search of Lost Genomes by Svante Pääbo – review

Svante Pääbo's pioneering exploration of ancient DNA may be about to reveal what makes us human

Svante Pääbo is the man who is rewriting the story of human evolution. From 1856, when the first Neanderthal skeleton was discovered in Germany, to the dawn of the 21st century, the map of our origins had to be pieced together entirely from fossils. All this changed with the coming of rapid DNA sequencing and the Human Genome Project.

Pääbo realised that if intact DNA could be recovered from Neanderthals (who became extinct about 30,000 years ago) and other early human ancestors, comparing the DNA of the genome with modern humans and great apes would dramatically increase the number of deductions that could be made concerning human evolution. Chimps can't speak, make fire or make weapons; Neanderthals had certainly mastered two of these (and probably the third) but it's likely that they lacked the genes and traits that account for our dominant role on the planet.

It was loudly trumpeted at the time of the announcement of the completion of the first human genome survey that we had "decoded the Book of Life". But decoding was the job that hadn't been done: the raw hieroglyphics had been discovered but not yet interpreted. This was a Rosetta Stone before the key had been found. It wasn't complete gibberish of course. In the 40 or so years since the genetic code for protein manufacture had been cracked, much had been already learned about many of the 24,000 or so human genes. But since it quickly became obvious that for every human gene there was an almost identical chimp gene (even mice are genetically more than 90% similar to us), the mystery of "what made us human" remained.

Pääbo's mission was to provide another of those "missing links" that have been so much a feature of the progress of evolutionary thought. He was probably singled out for this by an early passion, not for Neanderthals as such, but for mummified humans of a later date: the ancient Egyptians.

Pääbo is Swedish/Estonian, and is currently director of genetics at the Max Planck Institute for Evolutionary Anthropology in Leipzig. He is the founder of the field of ancient DNA studies; his father was a Nobel prize-winning biologist, Sune Bergström, and his mother, Karin Pääbo, an Estonian chemist. He was brought up by his mother and hardly knew his father, encountering him sometimes in the scientific literature.

Egyptology entered Pääbo's life when his mother took him to Egypt at the age of 13. Attending summer schools at the Mediterranean Museum in Stockholm, he realised that Egyptology was a ritual-bound slow-moving discipline; it was too sluggish for such a driven man.

Yet the lure of the mummies stayed with him. He studied medicine but was unsure whether to go on to practise or become a researcher. The latter won and he found himself in the late 70s at a leading molecular biology lab where gene sequencing was carried out. Enchanted by the power to read the code of DNA, he began to wonder if mummification allowed sufficient DNA to survive to allow sequencing. Mummies are 2,000-5,000 years old and comparing their DNA with that of people from modern Egypt could perhaps answer the question: what became of the ancient Egyptians? Was the population replaced by incomers or do some of their characteristic genes live on?

But the Egyptians were not as smart at preservation as we'd been led to believe: the mummies' DNA was badly degraded and Pääbo also came to realise that ancient human remains were often multiply overlaid with DNA from later human contact and bacterial contamination. To overcome this he began to develop techniques of ultra-cleanliness and adopted the new method of amplifying small pieces of DNA to make them readable.

Then in 1991 a well-preserved body was disgorged by a glacier in the Tyrol. Ötzi, as he was named, was 5,300 years old and Pääbo honed his technique on this serendipitous find. Ötzi's DNA was similar to that of any modern southern European, except that he lacked the mutation that allows adults to digest milk, a gene known to have spread rapidly in the past 5,000 years. Pääbo was working in Germany at the time, and his thoughts turned to Neanderthal man, a German icon. The first Neanderthal DNA sequences were published in 1997, but it took another 13 years of painstaking work before the landmark, full Neanderthal genome, based on three individuals, was published in a mammoth 174-page section of Science in May 2010.

The science of human evolution has been dogged by two opposing dogmas – the "Out of Africa" hypothesis and the "multiregional" hypothesis. Out of Africa, the dominant theory, claims that modern humans originated in Africa about 200,000 years ago, entered Europe, Asia and Polynesia 50-60,000 years ago (they seem to have reached Australia before Europe), by which time all other forms of proto-humans (hominins) were extinct or about to become so. It is known that the first hominin to leave Africa, Homo erectus, reached China by 1.8m years ago, so the multiregionalists believe that various groups of hominins coexisted from this time on and evolved in situ rather than only in Africa. Modern humans and Neanderthals diverged about 300,000 years ago and certainly met up again at some point, probably in the Middle East about 90-100,000 years ago, because modern Europeans and Asians, but not Africans, have 1.5-2.1% of Neanderthal DNA. Pääbo has shown that there was interbreeding between, at the present count, four distinct lines of hominin. So a hybrid of the two theories is now plausible: essentially Out of Africa but with some complicated interactions thereafter.

His book is also valuable for showing just how modern research teams work together and, sometimes, fall out. Along the way, a key collaborator became a competitor and, midstream, Pääbo abandoned one collaborating gene-sequencing company for another. The race for the Neanderthal genome is reminiscent of the human genome story of 10 years previously, as recounted in James Shreeve's The Genome War.

Now firmly established as the master of Neanderthal DNA, Pääbo continues to unravel the genome's deeper secrets. A recent major paper reports the best full Neanderthal sequence so far. Remarkably, modern humans have only 96 changes in protein-coding genes compared with Neanderthals. That is, almost every modern human across the world has these altered genes, so we can be sure they are significant. Several of them, not surprisingly, relate to brain development. We are edging closer and closer to an answer to that elusive question – what was it that made us human? Svante Pääbo will forever be celebrated as one of the pioneers.

• Peter Forbes and Tom Grimsey's Nanoscience: Giants of the Infinitesimal will be published by Papadakis in April.

• This article was amended on 20 February 2014 after an error in the editing process changed "Neanderthals had certainly mastered two of these (and probably the third)" to "Neanderthals had certainly mastered the first two of these". This has been corrected.


Peter Forbes

The GuardianTramp

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