How to give a Neanderthal a blood transfusion

It began as a joke. A paleoanthropologist, a geneticist and a blood specialist were hanging around an espresso machine – and one of them wondered: how would you give a Neanderthal a blood transfusion?

By the time they’d finished their short blacks and lattes, the researchers from the mixed lab at Aix-Marseille Université in France realised it was no joke: between them they had the tools to answer the question.

Today they report their surprising results in PLOS 1. For one thing, transfusing a Neanderthal with human blood would be a bad idea. Because of the mismatched Rh types, there’s a one-in-five chance of producing a baby with haemolytic disease. “That might explain why Neanderthal-human inbreeding was limited,” says paleoanthropologist and lead author Silvana Condemi. 

Blood types used to be the number one tool for tracing the story of human origins and migration. For instance in 1953 the origin of Native Americans was traced to Siberia based on the newly identified Diego blood group. But since the 1970s stretches of DNA code have replaced blood types as the preeminent tracking tool.

Today researchers have the complete genomes of at least 18 Neanderthals (only four with high ‘coverage’ – which refers to the number of times each nucleotide has been sequenced) and one Denisovan to pore over. They can study the genes for hair and eye colour, for their immune systems and disease vulnerabilities. But the genes for their blood types seem to have been neglected.

The Marseille coffee club decided to redress that gap. They focused on the seven major blood groups that are used today to match donors and recipients. Blood groups represent collections of tags – think of them like different-coloured ‘post its’ – that are carried on the surface of red blood cells. They consist of ABO, Rhesus (Rh), Kell, Duffy, Kidd, MNS and Diego. If these seven match up the transfusion will be successful. 

The authors took advantage of open access to drill down into the high-quality genomes of three Neanderthals and a Denisovan – for some reason all of them female. The Neanderthals included two Siberians: the 100,000 year old Altai female who lived in Denisova Cave, and a 48,000 year female who resided in Chagyrskaya Cave. A third female aged about 57,000 years came from Vindija Cave in Croatia. The Denisovan genome came from a female who lived in Denisova Cave about 64,000 years ago. 

The first surprise was discovering that the full variability of the ABO system seen in modern humans was present in the Neanderthals. “We thought for years that H. sapiens was the only one to have the full set,” says Condemi. That was because our closest relatives have only a partial set. Chimpanzees are all type A; gorillas are all type B. Until this study the only Neanderthal to be checked was blood type O. “So the assumption was they were all O,” says Condemi.

In fact the Vindija lady was a B (genotype BO), the Chagyrskaya lady an A (genotype AA), and the Altai lady A (genotype AA). The most parsimonious explanation, says Condemi, is that the African ancestor of Neanderthals and modern humans, perhaps Homo heidelbergensis, already possessed the full range of the ABO system.

The next surprise was that all three Neanderthals carried a rare Rhesus type which Condemi refers to as “Rhesus plus incomplete”. This variant had only ever been seen once before. In 2019, researchers analysing the DNA of 72 Western Desert Aboriginal people found that one of them carried the same novel Rhesus type. 

“At the time, it was assumed to be a new Rhesus type that had arisen in Australia,” says Condemi. “Now we know that it had existed in the past and was lost.”  The authors also found that in a population of 80 people from Papua New Guinea, only one carried this rare Rh type.

The finding confirms the evidence from DNA (all non-Africans carry about 2% Neanderthal DNA) that modern humans interbred with Neanderthals in the Middle East before heading to south Asia and Australia.

The blood-type findings also gives clues as to the Neanderthals’ disappearance.

First, there’s the finding that three Neanderthals separated by 50,000 years in time and 5,000 km of space all shared the same Rhesus type. This adds to the evidence from genome studies of their low genetic diversity, a factor that can put a species at risk of being wiped out by disease. 

On the other hand, interbreeding with modern humans could have put them at risk of another kind. 

Condemi says that if an Rh ‘partial complete’ Neanderthal mated with an Rh complete H. sapiens, there would be an 18% chance of the infant developing the condition known as “haemolytic disease of the newborn” and dying.

Bottom line: if you need to give a Neanderthal a blood transfusion, don’t use human blood unless it’s from a rare Western Desert Australian or Papuan.