Svante Pääbo has a book out, Neanderthal Man, in which he recounts his adventures sequencing ancient DNA. He has had three big successes: the first successful sequencing of Neanderthal mtDNA in 1997, the first sequencing of the Neanderthal nuclear genome, and later the first Denisovan genome.
Ancient DNA is usually very degraded: short DNA sequences mixed with bacterial DNA, and often contaminated by modern human DNA. Pääbo and his team made major contributions in sample preparation and sequencing methodology. The interpretation of that data has been performed by people like David Reich, Nick Patterson, and Monty Slatkin – and a good thing too, because Pääbo is no theorist. At each stage of his work, he had certain expectations about the results, and those expectations were nearly always wrong. He thought any Neanderthal genetic contribution to modern humans was very unlikely – but it’s there. To be fair, that was the case for many other people working in human genetics. I’ve never really understood why.
Or later, after a few-percent Neanderthal admixture had been shown to exist in people outside of sub-Saharan Africa, he at first thought that it probably had no functional consequences. He believed that the correct null hypothesis was that a genetic change would have no consequences whatever: but that’s silly. The question wasn’t whether one particular Neanderthal allele was advantageous, but whether any of them were. In order for his null model to be correct, Neanderthals would had to be inferior indeed, not better adapted to their home territories in any way. Although again, to be fair, there are whole branches of science in which the favorite null model is always wrong.
One interesting side point: by looking at the entrails of the online supplement to the big Neanderthal paper in May 2010, it was possible to see that there was something odd about Melanesians: they were genetically more distant from Africans than other Eurasians. Which implied another dose of archaic ancestry. Judging from this book (which may not have the complete story) the people working that problem didn’t notice that anomaly, but instead compared against the just-sequenced Denisovan genome and noticed that Melanesians were significantly closer to Denisovans than other Eurasians.
A good experimentalist can (sometimes) get to some reasonable approximation of the truth even if he’s short on theory. Worth remembering, particularly in the human sciences, where emotions make theory gang aft a-gley.