The analysis of DNA to create genetic profiles of an organism sounds like a relatively unremarkable exercise these days. But that is when the DNA samples are readily available.
Obtaining genetic information of organisms that went extinct thousands of years ago can be extremely difficult, mainly because of the complications in collecting their DNA. While it is possible to extract DNA samples from fossil and remains, it is not as straightforward as getting it from organisms that inhabited the earth in more contemporary times.
This year’s Nobel Prize for medicine has gone to a scientist who is credited with developing new and innovative methodologies to extract ‘clean’ DNA from human fossil tens of thousands of years old, and reading the genetic information contained therein.
These methodologies enabled the 67-year-old Svante Paabo, a Swedish scientist based in Germany, to piece together the genome sequence of the Neanderthal, modern human’s cousin species that went extinct about 30,000 years ago, and offer new evidence on the interactions of Neanderthals with ancestors of modern human beings. What Paabo had accomplished was ‘seemingly impossible’, the Nobel Prize committee said in its citation.
In the process, Paabo, who runs the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, also discovered the existence of an unknown sub-species of the human family, now called Denisovans, who lived around the same time as the Neanderthals.
In fact, the ancestors of modern humans, Neanderthals and Denisovans co-existed for about 20,000 years, during which they not only interacted with each other, but also inter-bred, Paabo’s research has shown. In some populations of modern human beings, between one and three per cent of the genome has been found to originate from the Neanderthals.
“His main contribution has been in developing the research methodologies to extract DNA samples from very old remains. He has really been the leader in this, and his methodologies provided the essential breakthrough for his work on comparison of Neanderthal genomes with the modern man,” said Professor Vasant Shinde, a former vice-chancellor of Pune-based Deccan College (deemed university) who himself has employed similar techniques at the Rakhigarhi excavation site in Haryana and come up with groundbreaking findings about ancient populations in the Indian region.
“We have been dealing with remains that are about 5,000 years old. Our methodology is slightly different from Paabo’s, and is suitable for obtaining DNA from relics up to 10,000 years old. But the objective is the same,” Shinde told The Indian Express. Shinde revealed that Paabo, in fact, had reached out to him in 2015 for collaboration on the Rakhigarhi project.
“By that time, we had already been collaborating with a research team at Harvard led by David Reich. But Paabo has been extremely interested in Rakhigarhi and has closely followed the work there. The Nobel Prize to Paabo is a much-needed recognition for the kind of scientific investigations we indulge in,” he said.
Dr J Gowrishankar, director of IISER Mohali, said what Paabo had essentially done was to replace indirect evidence in the genetic studies of archaeological remains with direct observational evidence.
“Earlier, scientists were studying the genomes of current human beings and extrapolating the information into the past. It is called deduction. While this is a scientifically valid exercise, it is indirect and involves uncertainties. Paabo developed methodologies that have eliminated deductions, and rely on direct observation. For example, he realised that one particular skull bone, called petrous, preserves DNA better than the rest of the body. This was a very useful revelation,” Gowrishankar, a former head of Hyderabad-based Centre for DNA Fingerprinting and Diagnostics (CDFD), said.
Dr K Thangaraj, the present director of CDFD, said Paabo was immensely successful in getting meaningful information from DNA samples contaminated with a lot of ‘impurities’ over time, including the possibility of DNA from latter day human beings who might have interacted with the fossil.
“In a way, he came up with a very efficient algorithm to get only the Neanderthal DNA. The fact that he was dealing with skeletal remains in Europe did help him because unlike in tropical climates in India, the bones and skeletons are much better preserved in colder climates. But there were so many other teams that have been working on this, and making very important contributions. Paabo did stand out with his methodologies,” Thangaraj, who has been involved with similar work in India, including at Rakhigarhi, said.
Gowrishankar said the evidence that Paabo produced for the interbreeding between the different sub-species of human beings in ancient times was remarkable. “He identified a skeleton of a human whose father was a Neanderthal and the mother a Denisovan. In another case, he showed that a skeleton was four generations subsequent to the mating between a Neanderthal and ancestors of modern humans. All this can be established through genetics,” he said.
Establishing the genetic evolution of human beings can have important implications for medical science, the reason why Paabo’s work has been awarded the Nobel Prize. “This ancient flow of genes to present day humans has physiological relevance today, for example affecting how our immune system reacts to infections,” the Nobel Prize committee said.
In fact, Paabo published two papers, in 2020 and in 2021, on the possibility of genes from Neanderthals influencing the susceptibility of human beings to Covid. In the 2020 paper, published in Nature, he showed that one particular gene from the Neanderthals aggravated the risk of severe diseases among Covid patients. In the other paper, published in the Proceedings of the National Academy of Sciences, he showed that another gene from the Neanderthals was possibly offering protection against severe Covid.“These are two different genes located at different places in the sequence. So, it wasn’t as if he was contradicting himself,” Gowrishankar said.
Incidentally, Paabo’s father, Sune K Bergstrom, is also a winner of Nobel Prize in Physiology, making them only the sixth father-son pair to have won a Nobel each. A 2014 profile of Paabo in The New York Times, shortly after the publication of his bestselling book ‘Neanderthal Man’, described how the scientist had revealed, “three quarters of the way through the book”, that he was Bergstrom’s son. “I had grown up as the secret extramarital son of Sune Bergstrom, a well-known biochemist who had shared the Nobel Prize in 1982,” Paabo wrote.