Most recently this letter to Brad DeLong, published on Brad's blog, is a great advert for the book (emphases mine) ...
Grasping Reality with Both Hands: Brad DeLong's Semi-Daily JournalThe thesis, in short, is that the pre-euro population of the Americas was tens of millions of people, perhaps 100 million. A larger population than the Europe of that time.
... Pennington correctly observes that I "barely mentioned the horrible [e]ffects of the wars that went on between the whites and indians." This is because I was writing about demography and demographically they didn't amount to much. By the 18th century, disease had already wiped out 75-95% of the native population of the Americas. Indian warfare, awful as it often was, simply piled on another few percentage points to the mortality count.... As the historian Alfred Crosby has repeatedly observed, societies tend to measure "progress" in terms of things that they are good at. Europeans were good at making metal tools and devices, so we tend to look for them -- Indians didn't have steel axes and geared machines, so they must be inferior. But many Indian societies were extremely deft about agriculture. Looking at a Europe afflicted by recurrent famine, one can imagine them viewing these societies as so undeveloped that they were unable to feed themselves. It's hard to say which view is correct.
...many European innovations were directly related to the existence of domestic animals. At the time of its construction, the Roman highway system had no direct equivalent in the Americas. Paved roads are obviously a sign of technological development, because you need them for large-scale transportation, right? But it would have been nuts for Indians to have built such roads, because they didn't have wheeled vehicles. And they didn't have wheeled vehicles (except as toys) because they didn't have horses, and they evidently calculated that the small gains in efficiency for human-powered vehicles was not worth the large costs in labor and materials to build highways, especially when rivers were an attractive alternative. (Compared to Europe, much of the Americas is river-rich.) So does this mean that Native America was less developed?
Lauren Tombari asks, "Wouldn´t there be some evidence of the many towns Desoto saw? Would there be ~100 million graves from the 95% death rate?" She will be happy to learn there is lots of evidence of the many towns seen by DeSoto. Although it is inexplicably absent from US history textbooks, there were literally thousands of mound cities and towns in the US Southeast and the Mississippi valley. Many have been destroyed, but my book, 1491, has a map of some of the main sites that remain. About the graves: the answer is no. In epidemics, people generally aren't buried, but left to die where they fall. The vast majority of those skeletons simply vanish. An example of this is the slaughter of the buffalo. We know from abundant historical records that less than 150 years ago hunters killed millions of bison in the Great Plains. Yet if you drive around there now, you don't see heaps of bones. The same, alas, happened to Indians. Of course it didn't happen to every Indian -- and there are many, many known Indian graveyards, so many that the federal government has passed special legislation to protect them.
... In this country, the French, Spanish, Dutch and English made more than 20 attempts to found colonies before the Pilgrims. All but one of them failed. The exception was Jamestown, in which almost 5 out of 6 colonists sent in the first 15 years died -- something that most people would regard as a failure. (St. Augustine, in Florida, was founded before Plimoth, but it was abandoned for years before being resettled, so I would count it as a failure, too.) Then comes the epidemic in New England, and suddenly, beginning with the Pilgrims, almost every English colony survives and thrives.
A possible counter-argument would be to ask why then did Amerindians not have their equivalent of the Euro's embedded bio-weapons? A population of that size should be able to support some very nasty viruses.
The Atlantic article argues that humans disseminated throughout the Americans long before 12,000 BCE, however I think recent gene data supports the 12,000 BCE date for all living descendants of the first people. Animal extinction and canine genomic data may also support the 12,000 BCE date. If 12,000 BCE is in fact the date for entrance to the Americas, that might also argue against such a vast population.
See also: Squanto's story, European rat plagues kill American rats, Mann's 2004 NYT essay, European dog diseases kill American dogs.
Regardless of the original population the euro "conquest" (inheritance, almost) of the Americas is an abject lesson in the awesome power of biological WMDs.