by Karin Bojs
Through his studies of ancient DNA, Swedish-born Svante Pääbo has done more than anyone else to shed light on the early history of humankind. Today he is one of the world’s most renowned scientists and the director of the department of evolutionary genetics at the Max Planck Institute for Evolutionary Anthropology, of which he is a co-founder, in the German city of Leipzig.
I visited the Institute twice while working on this book. It is housed in a specially designed, spacious building, with light flooding in through glass walls. A pool encircled by green plants gleams in a central atrium. At the entrance there is a climbing wall four storeys high, built to Pääbo’s specifications. This is used by young researchers training for African fieldwork on treetop-dwelling monkeys. Next to the climbing wall stands a grand piano which is used for choir practice. These features go to show some of the Institute’s unique character. Researchers here work in disciplines as diverse as psychology, palaeontology and linguistics, seeking to develop an understanding of how we came to be the people we are today. But it is molecular biology and DNA research that lie at the very heart of the Institute’s work.
The special laboratory for extracting ancient DNA is situated in the basement, to avoid any unwanted contamination. It is here that Pääbo and his young colleagues strive to further refine their technology. Although they now have many competitors in other countries, the Leipzig group is still a world leader. During the week when I visited the Institute for the second time, they published a study on DNA from an archaic human found in Spain, some 400,000 years old – from a time before even the Neanderthals had emerged.
Pääbo’s work is cutting-edge research that drives progress in technology and knowledge. But the fact remains that it was the Neanderthals that made him famous, and it is his increasingly high-resolution analyses of Neanderthal DNA that have made him known to the general public.
When I entered Pääbo’s office, the first thing to meet my eyes was a Neanderthal skeleton, squeezed in between the desk and the sofa. It was a composite, made up of copies of various excavated bones. In contrast to the short, powerfully built Neanderthal, Pääbo was tall and lanky, with a long, narrow face.
Newspapers worldwide have dedicated metres of column space to his research and his unusual family background as the secret, illegitimate son of Sune Bergström, the Nobel Prize-winning vice-chancellor (or president, in US terminology) of Stockholm’s Karolinska Institute. Pääbo himself has written an interesting autobiography, Neanderthal Man, in which he focuses more on his mother, the Estonian refugee and food chemist Karin Pääbo. When he was 13, she took him on a journey to Egypt, where he was seized by a deep fascination with mummies. That was how his career in research began.
He grew up in Bagarmossen, a suburb south of Stockholm, learned Russian at the Swedish Armed Forces’ Language Institute (one of their most demanding courses) and went on to study Egyptology and Coptic at Uppsala University. A few years later, he abandoned Egyptology and switched to medical training. After four years of medicine, he began to conduct research in cell biology.
His day-to-day job involved studying a viral protein. In secret, he was also trying to isolate DNA from mummies thousands of years old. His boss knew nothing of this until Pääbo’s first scientific article was well on the way to publication. The article appeared in an East German journal because the first mummies Pääbo had investigated came from a museum in East Berlin. It later transpired that what Pääbo had thought to be sensational DNA from a mummy was probably mostly the result of contamination by our contemporaries. But at least the idea was there. He had shown that DNA can survive in tissues several millennia old.
No one in the West took any notice of the East German publication. However, one year later Pääbo published another article, this time in the British journal Nature. This, by contrast, attracted great attention. One of the consequences was a letter from Allan Wilson of the University of Berkeley in California, one of the world’s foremost specialists in evolution and DNA at that time. Wilson asked whether he could come and work in ‘Professor’ Pääbo’s laboratory. Pääbo, who had just turned 30, was still working on his doctoral thesis, and he was far from having a lab to call his own. Instead, it was agreed that Pääbo would come and research at Wilson’s laboratory in California, where Wilson and his colleagues had started to use DNA technology to unravel the early history of humankind.
By 1987 they were able to publish the first study using DNA technology to show that everyone living now ultimately originates from Africa. Our common foremother was a woman living in Africa some 200,000 years ago, who is usually known as ‘mitochondrial Eve’. The name, of course, is a nod to the biblical creation myth. Mitochondria are discrete structures within cells that contain a small amount of DNA. Initially, all DNA analyses of the origins of humankind were based solely on mitochondrial DNA. This is because it is much easier to analyse than DNA from the cell nucleus (nuclear DNA), there being thousands of mitochondria in most cells, but only one nucleus. One limitation is that mitochondrial DNA can only be used to trace the origins of an individual in the maternal line, as we inherit our mitochondria solely from our mothers.
So by 1987, the technology available was already sophisticated enough to trace ‘mitochondrial Eve’, though the methods that were used appear unbelievably labour-intensive by today’s standards. The young researchers from Wilson’s laboratory visited maternity hospitals all over California to collect placentas from women from different parts of the world. Laboriously, they isolated the DNA from these placentas and calculated the results with their primitive computers.
Linda Vigilant, who is now married to Svante Pääbo, was one of Allan Wilson’s postgraduate students. She conducted a follow-up study of mitochondrial Eve a few years later. The low-performance computers of the time were still so slow that it took a week to perform the calculations.
Figure 1 Foremothers of Africa. ‘Eve’, who lived in Africa around 200,000 years ago, became the foremother of everyone living today. About 60,000 years ago, one of the lines of her descendants left Africa and subsequently dispersed worldwide.
But DNA technology had moved on considerably. A researcher in California had developed a technique for copying DNA, known as PCR (polymerase chain reaction), for which he was awarded the Nobel Prize a few years later. This method enabled researchers to work on single strands of hair, rather than having to use an entire placenta. Anthropologists from all over the world helped to supply strands of hair from a very wide range of populations. And the results of the first study were confirmed. About 200,000 years ago, there was a woman in Africa from whom everyone alive today is descended. She was thus our common foremother.
A few years later, in 1995, American researchers published their findings about mitochondrial Eve’s male counterpart, known as ‘Y-chromosome Adam’. Thanks to improved DNA technology and increasingly powerful computers, the Y chromosomes of men from all over the world could now be compared. Y chromosomes contain far more DNA than mitochondria, and they are passed on from father to son only. This means they can only be used to reconstruct the direct paternal line in a family tree. The results revealed that a man living about 200,000 years ago was the forefather of all men living today. Y-chromosome Adam lived in Africa too.
There was no longer any room for doubt. The multi-regional theory was dead. The origins of modern humans lie in Africa.
DNA technology advanced in leaps and bounds. Pääbo and others succeeded in developing methods for analysing samples several thousands of years old. By conducting tests on animal fossils, he learned how to keep samples uncontaminated. The challenge was to exclude any dust, old bacteria or traces left by people who had touched the fossils in recent times.
After California, he was offered a post as a professor at a zoological institution in Munich. There he impressed on his two doctoral students that they must avoid all forms of contamination, irradiate the whole laboratory with ultraviolet light every night, go straight to the special laboratory every morning wi
thout visiting any other laboratories with DNA samples, and take a whole range of other precautions.
In the summer of 1997 Pääbo published a DNA analysis of the world’s most famous Neanderthal – the very skeleton that had been discovered in the Neander Valley in the mid-nineteenth century, giving Neanderthals their name. This time, the results were far more reliable than those obtained from the ancient mummy 12 years previously. The analysis, based on mitochondrial DNA, showed clearly that Neanderthals cannot be the forebears of modern Europeans. We are not their great-grandchildren; at least, we are not descended directly from them in the maternal line. It would be more accurate to compare our relationship with that of two groups of cousins whose common origins lie much further back in history.
This study had an enormous impact. Pääbo became a science superstar, particularly in Germany, where Neanderthals have had a unique status since they were first discovered in the nineteenth century.
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Unfortunately, I have to admit I missed the news about this revolutionary study. I had started my job as Dagens Nyheter’s science editor just a few months previously and had not yet had time to acquaint myself with all the journals a science journalist needs to monitor. Nor was I yet on the right lists to receive advance warning of press conferences, and invitations to them.
But a few weeks later I met Pääbo at a seminar on the new gene technology, held in Oslo. We had dinner together, and my interest in this field of research was fired. Since then I have interviewed Pääbo many times, attended his lectures and reported in Dagens Nyheter on the publication of his studies in the world’s leading scientific journals.
After the first mitochondrial analyses, he went on to analyse nuclear DNA, which, as noted above, is far trickier. However, a successful analysis helps provide a far fuller picture, as mitochondria contain no more than a few thousandths of a per cent of our total DNA. Moreover, they can only be passed on through the maternal line. The rest of our DNA, located in the cell nucleus, is inherited from both parents.
The first preliminary mapping of nuclear DNA published by Pääbo and his team in 2009 confirmed the picture that had emerged from the first analysis of mitochondrial DNA – that Neanderthals are not the forebears of modern humans. Rather, they should be seen as our genetic cousins.
But then came further input. More sophisticated analyses brought unexpected results. Pääbo himself was startled. In May 2010 he and his collaborators published an exhaustive analysis showing that Neanderthals and modern humans had in fact produced offspring. Features inherited from Neanderthals live on in us; the Neanderthals are not completely extinct.
Since then, the technology available for analysing prehistoric DNA has advanced even further, and it can now produce as high-definition an image as if researchers had examined you or me. The conclusions they have drawn can be summarised as follows.
It turns out that Neanderthals are our forebears after all, though they account for only about 2 per cent of our genetic make-up. When anatomically modern humans migrated from Africa to other parts of the world, they passed through the Middle East, including the region of today’s Israel known as Galilee. The area was already inhabited by Neanderthals. They must have lived in parallel with anatomically modern humans in the same region for some time. People from the two groups had sex with each other on a number of occasions, producing offspring who were able to have healthy children themselves.
Modern-day people whose origins lie in Asia, Australia and the Americas have slightly more Neanderthal DNA than Europeans. Just over 2 per cent of their DNA is of Neanderthal origin, while an average European has just less than 2 per cent. This is probably the result of further interbreeding between Neanderthals and modern humans further east in Asia.
Moreover, the people who migrated eastwards into Asia, New Guinea and Australia appear to have interbred with another kind of archaic human called the Denisovans. Modern inhabitants of New Guinea have up to 6 per cent Denisovan DNA in their genetic make-up, and a smaller percentage can also be found in the Chinese population.
Characteristics inherited from Neanderthals can be detected even among Africans. This applies even to traditional groups such as the Yoruba of West Africa and the Mbuti people of the Democratic Republic of the Congo. However, the proportion is minute in such cases, and can be explained by the fact that some Europeans and Asians returned to Africa in the course of history.
There are commercial firms today selling DNA tests that, they claim, can reveal the percentage of Neanderthal or Denisovan DNA in an individual’s genetic make-up. But Pääbo describes these tests as unreliable. The margin of error is so great that the result is next to meaningless. In retrospect, he regrets that his own team failed to apply for a patent on such tests; they would have been able to guarantee far higher standards.
Presumably it was an advantage for a young child living in the Middle East 54,000 years ago to have inherited certain features from Neanderthals. Such children may well have been healthier and more resistant to infection than others. Those of our forebears who migrated from Africa to the Middle East were part of a small group, possibly just a few dozen or a few hundred individuals. A few generations of breeding solely within the group had seriously depleted their immune defence. Inbreeding is bad for immune defence, so it is a good thing to have new, fresh blood from outside.
The American immunologist Peter Parham has identified a group of genes in our immune system that appear to have been inherited from Neanderthals. These genes must have helped the Troll Child and his peers to survive 54,000 years ago. Today, the same genes may be partly responsible for making the immune system too effective; as a result, it goes haywire in some cases, increasing the risk of autoimmune diseases such as multiple sclerosis and type 1 diabetes.
Researchers have identified two Neanderthal genes that affect the capacity to transform fat in the diet. In our time, bearing one of these two genes increases the risk of contracting type 2 diabetes. This disease is closely linked with being overweight, a major problem today. But things were different 54,000 years ago. For the first modern Europeans, it was an advantage for their bodies to be able to assimilate as much fat as possible; that reduced the risk of dying of starvation.
Svante Pääbo’s research team has also identified a handful of other genes that seem to have been transferred from Neanderthals to modern human beings. They all affect a substance called keratin in our hair and skin. Both Asians and Europeans seem to have inherited variants of these keratin genes from the Neanderthals, but oddly enough, the sets of keratin genes concerned are different. It is not yet clear exactly how Neanderthal genes affect our hair and skin. If I were going to lay a bet, however, I would wager that straight hair is one of the characteristics inherited from the Neanderthals.
Pääbo himself prefers not to speculate about the appearance of Neanderthals’ hair and skin. Today, other DNA researchers have developed genetic tests that provide clues about the colour of their skin, eyes and hair. A Spanish research team claims to have identified the hereditary disposition for red hair in one Neanderthal individual. Pääbo, however, thinks these tests are still far too unreliable for him to publish such information. During our interview I tried to press him on this point, arguing that the colour of Neanderthals’ eyes, skin and hair would be sure to interest the general public. This kind of information would give a more vivid picture of what we experienced when we encountered Neanderthals.
Pääbo was not swayed by this argument. However, he did reveal something that has not yet been published: none of the Neanderthals he has analysed himself seem to have the genetic make-up associated with red hair. The Neanderthal individual that he has examined using the most high-resolution analysis, found in a Siberian cave, was probably dark-haired.
He was more comfortable talking about the approximately 87 gene variants that, though present in nearly all modern people, have not so far been found in any Neanderthals. The gene that has been researched in most detail is known as F
OXP2.
There is a family living in Britain with several members of different generations who all have a serious language disability. All these individuals have a flaw in this particular gene, which clearly affects the ability to speak. This gene differs in just one small point between mice and chimpanzees. The difference between chimps and Neanderthals amounts to two points. In principle, modern humans and Neanderthals have identical FOXP2 genes. However, there is one tiny difference, discovered by Pääbo and his collaborators. It was difficult to find, being located well outside the gene itself, but it appears to have a significant impact on how the gene functions.
The Leipzig research group has developed special experimental mice bearing the human variant of the FOXP2 gene. Their squeaks are different from those of ordinary mice, and they have better memories. The difference lies in a particular kind of memory known to psychologists as ‘procedural memory’. It involves the same mechanism we use when learning to ride a bike or dance; to begin with we have to think about each individual movement, but after a while we have internalised them. We have them at our fingertips – or rather in our cerebellum. We can make the movement automatically, without having to think about it. Learning to speak is no different.
It is reasonable to conclude that Neanderthal people could also talk to each other at some level – but not as we can.
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Svante Pääbo tries to stick scrupulously to his scientific findings and to avoid speculation. However, there is a person who has not suffered from any such hang-ups when it comes to speculating about our encounters with Neanderthals – the American author Jean M. Auel. Her books, starting with The Clan of the Cave Bear, have sold in their millions. The first book in the series, which came out in 1980, describes how orphan Ayla is cared for by a different race of people. When Ayla grows up, she is repeatedly raped by the clan chief’s son and gives birth to a son who is thus half Neanderthal, half modern human – this is known as a hybrid.
