120,000-year-old tumour found in Neanderthal rib

Many tumours in modern humans are caused by exposure to toxins, pollution, radiation and unhealthy diets over a long period of time. Thus, it’s remarkably rare to find evidence of these in prehistoric populations in the human evolutionary line: Our ancient ancestors experienced relatively short lives in a pristine environment. Also, tumours in fleshy tissue decay and generally aren’t fossilized, so they’re difficult for archaeologists to find.

The large lesion is located above the tubercular facet and extends laterally. The trabeculae have been destroyed and the cortex appears expansive. The thin cortical bone forming the superior surface of the cavern was broken away postmortem. (b) Krapina 120.6 shows the normal pattern of bony trabeculae in the medullary space. The surface irregularities are post-mortem. doi:10.1371/journal.pone.0064539.g001

That’s what’s extraordinary about the news that a team of researchers has identified evidence of fibrous dysplasia, in the rib of a 120,000-year-old Neanderthal from Krapina, Croatia. The findings are included in the forthcoming edition of PLoS ONE.

Fibrous dysplasia is an uncommon, benign disorder characterized by a tumour-like proliferation of fibro-osseous tissue. The cause of fibrous dysplasia is still unknown and most cases display no particular pattern of inheritance. This tumour is normally solitary that arises during periods of bone growth in older children and adolescents and slowly enlarges. Most modern patients are diagnosed with fibrous dysplasia in the first three decades of life.

100,000 years older

“It’s evidence that Neanderthals suffered tumours — that they were susceptible to the same kinds of diseases that we see in modern humans,” said David Frayer, professor of anthropology at the University of Kansas, who co-authored the paper. “Before this, the earliest tumour in bone that we’ve seen goes back to an Egyptian mummy. So this is 100,000 years older than the previous tumour that has been found.”

The bone where the tumour was discovered isn’t associated with a complete skeleton, Frayer said. So researchers don’t know if the tumour afflicted a male or female, or precisely how old the adult individual was at the time of death, or even the cause of death.

“It may have involved other bones of the skeleton, but none of those have been found,” said Frayer. “At this site, there are more than 900 bones, but very few of them are associated one with the other. And while there are other pathologies, none of the others show evidence of a tumour.”

Two views of Krapina 120.71 rib fragment: a: Superior/inferior radiograph view of Krapina 120.71 in position matching illustration in Figure 1; b: Lateral view in position matching the µ-CT scan series in Figure 3. The radiograph shows the full extent of the bony cavern excavated by the growth of the dysplastic mass. The lesion occupies most of the length of the fragment, but does not extend beyond the medial and distal borders. The full extent of the lesion is visible within this small rib fragment. doi:10.1371/journal.pone.0064539.g002

Unique genes passed on to modern humans

For years, most scientists were convinced that Neanderthals didn’t factor into the evolutionary line that results in modern humans. However, within the past decade, genetic analysis has revealed that Neanderthals were forefathers of present-day peoples.

“We have actual nuclear DNA from a number of different Neanderthals — not complete sequences — but segments of nuclear DNA,” said Frayer. “So we know that Neanderthals have a set of unique genes that were passed on to modern humans. It’s about 4 percent of our genetic make-up.”

A fairly large tumour

According to the researchers, the Neanderthal bone from Krapina, Croatia, is a 30-millimetre-long fragment of the left rib that shows a fresh break. The break in the rib exposes a chamber that is 18 millimetres in length and 7.6 millimetres wide. This cavity in the bone is highly unusual — ordinarily a rib is packed with cancellous bone — and, after analysis with radiograph and CT scans, the investigators came to believe it was the site of a benign tumour associated with fibrous dysplasia.

Fibrous dysplasia “is a developmental disorder of bone in which lesions develop fibrous tissue and spicules of woven bone,” the researchers write. However, it’s difficult to know for certain how severely the tumour affected the Neanderthal individual.

“It wasn’t a small tumour,” Frayer said. “It was a fairly large one, probably bulging at the base of the rib. We’re not sure how far along it was, but it was well-expressed in the bone. It was in the upper third of the back, and muscles attach there that are associated with raising the arm.”

Association of humans to neoplastic disease

Neoplastic bone disease, of both primary and secondary origin, is an exceptionally rare occurrence in the evolutionary fossil and archaeological record of human prehistory, until now extending back in time only 1,000–4,000 years – this takes the occurrence of tumours well into the past and on a different line from our own ancestors.

It has long been recognized that environmental changes wrought by humans, compounded by population expansion, have resulted in an increase in the types and the intensification of the pollutants within the environment, many of which are directly associated with neoplastic disease and were not part of environments in the past – this new discovery provides insights into the nature and history of the association of humans to neoplastic disease.

Frayer’s colleagues on the paper are Janet Monge and Morrie Kricun of the University of Pennsylvania, Alan Mann of Princeton University, and Jakov Radovcic and Davorka Radovcic of the Croatian Natural History Museum.

Source: The University of Kansas