A hymn of courage: One article to understand the 2022 Nobel Prize in Physiology or Medicine

▎WuXi AppTec Content Team Editor

Yesterday afternoon,

2022 Nobel Prize in Physiology or Medicine

Awarded to Professor Svante Pääbo for his outstanding contributions to the field of paleogenomics. Many people say that this year’s Nobel Prize is somewhat unpopular, but as long as you understand Professor Pabo’s work, you will know that his research is of great significance to human understanding and is inextricably linked to the health of modern human beings. In today’s article, the WuXi AppTec content team will join you in getting closer to the new Nobel Laureate to learn about his life and research.

▲This year’s Nobel Prize winner Dr. Svante Pääbo(Image source: Reference [2])

Nuo second generation who struggled to reconcile with father

Professor Pabo works at the Max Planck Institute in Germany, where October 3rd is a local holiday to commemorate the reunification of the two Germanys. When he finished his last sip of tea and wanted to pick up his daughter from his mother-in-law’s house, a call came from Sweden. For a split second, he thought there was something wrong with his holiday cabin in Sweden, something like a broken lawn mower. He was surprised when he got the news of the award. In the subsequent interview, he admitted that although he has won many awards, he never thought that his work on ancient human genomics could be included in the Nobel Prize.

▲The official account of the Nobel Prize said that Professor Pabo was drinking coffee when he heard the news of the award (Professor Pabo said he was drinking tea instead) (Image credit: Nobel Prize official Twitter; Credit: Linda Vigilant)

Pabo grew up in Stockholm, and the Nobel committee proudly announced that we welcomed a Swedish laureate this year. His mother, a refugee from Estonia, had an extreme love for science. She worked in the group of a biochemist named Sune Bergström, who had his own independent family but became Pabo’s biological father in an extramarital affair. In 1982, Bergström shared the Nobel Prize in Physiology or Medicine for the discovery of the physiological role of prostaglandins and similar hormones. From this point of view, Pabo can be said to be the second generation of Nuo.

A New Yorker report in 2011 mentioned that Bergström would take the young Pabo in the name of his work every Saturday, where he would not worry about being recognized. walk. His wife also tacitly never called him “working hours” on Saturdays, hoping to keep the secret under seal. Bergström’s half-brother, Pabo, was not known to his son until shortly before his death.

▲Father, who is also a Nobel laureate, did not have as much influence on Pabo as he thought (Photo credit: Sune K. Bergström – Facts. NobelPrize.org. Nobel Prize Outreach AB 2022. Mon. 3 Oct 2022.)

The interview of the Nobel Prize Committee jokingly mentioned Pabo’s Nobel Prize bloodline, and asked whether it was a different feeling to win the Nobel Prize as the second generation of Nobel Prize winners. Pabo was silent for a few seconds after hearing the question, sighed deeply, and then hesitated to suggest that his father didn’t have that much influence on him. In fact, he even regretted that his mother could not witness this day, because she inspired him to grow up on the path of science.

Fascinated by history

From an early age, Pabo was interested in things with a sense of history. In the dense forests of Sweden, he sometimes finds shards of pottery left by prehistoric people and uses them to decorate his room. Once, his mother took him on a tour of Egypt. After seeing the pyramid, the young Pabo was even more fascinated by it. In college, he aspired to be an Egyptologist.

But college courses were a little different than he had imagined. Originally he wanted to study mummies, but the course only arranged to analyze hieroglyphs. Bored by this, Pabo decided to study medicine and cell biology, but he never forgot his love for mummies. His doctorate was about virus research, but he secretly researched the method of extracting DNA from ancient mummies without telling his supervisor.

Because he was afraid that his mentor would think he was not doing his job properly, even if he successfully extracted DNA from a mummified child, he only dared to vote for an unknown small magazine to avoid causing trouble.No. But the quality of this paper, which I tinkered with in my spare time, is extremely high. After sharing the paper with Professor Allan Wilson, a well-known biochemist at the University of California, Berkeley, for advice, the latter was amazed by the content of the paper and mistook Pabo as a young professor, and wrote back asking if he could come to him lab visits. Pabo had no choice but to write back that not only did he not have a laboratory, but he hadn’t even gotten his Ph.D.

Image source: 123RF

Finally, Pabo’s paper was edited into English, published as a cover article in Nature, and published by Time The Weekly reported that it was “one of the greatest recent achievements in the use of molecular biology”. Pabo’s colleagues in Sweden disagreed, urging him to stop wasting time on his strange hobby of mummification, and return to work on viruses.

Pabo didn’t hesitate to leave Sweden for California to join Professor Wilson’s lab. They share the same interest in ancient DNA.

Mission Impossible

In the official press release of the Nobel Prize, Professor Pabo’s genetic sequencing of ancient humans was called “mission impossible.” This is because the natural chemical nature of DNA means that it is easily degraded and can also be contaminated with DNA from modern humans and even bacteria. To find the few ancient human samples, extract the little DNA left from them, decontaminate them, and analyze them accurately does sound impossible.

▲DNA is located in two different locations within the cell: DNA in the nucleus contains most of the genetic information, and the rest is located in the mitochondria. After the death of ancient humans, DNA degrades over time and is also contaminated with DNA from bacteria and contemporary humans (Image source: Reference [1])

That was the big challenge Pabo faced when he first arrived in California. The DNA of ancient Egyptians is very close to that of modern people, and even some fragments are exactly the same. How do we make the distinction? In order to make a technological breakthrough, he chose to use DNA from extinct animals to practice his hands, ranging from giant sloths and mammoths that disappeared tens of thousands of years ago to Tasmanian tigers that have only been extinct for decades . In the course of these explorations, Professor Pabo has opened up a whole new field of paleogenomics.

He is highly regarded by colleagues who work with him, saying that he has turned sci-fi like Jurassic Park into real science,and without Professor Pabo, Nor will paleogenomics. Rarely, Professor Pabo remained humble enough to say it was the team’s contribution, not just him.

A few years later, Professor Pabo received a call from the Rheinland Museum in Germany, asking if it was possible to extract useful DNA from some ancient samples, and he replied It is impossible to know whether the sample is still intact unless the sample can be analyzed for dissolution, and the probability of success is only about 5%.

A few months later, he received a small piece of the humerus from the archaic Homo sapiens, the Neanderthals that would later make Professor Pabo famous.


The original Neanderthal specimens were found in a limestone cave in Germany, not taken seriously and disposed of as garbage for a time until they were completely intact Almost certainly at a big discount. A local businessman rescued the remaining bone fragments and handed them over to a fossil collector who saw traces of humans in them. It was shortly after Darwin published On the Origin of Species, and the shattered bone fragments also sparked a long-running debate about the origin of humans.

More and more complete Neanderthal skeletons were later found. Despite their thicker bones and oddly shaped skulls, anatomists have seen too many similarities to the human skeleton, thinking if Neanderthals lived to this day, walking into New York In the city’s subway, people around him won’t pay much attention to him.

▲Neanderthals are very similar to modern humans (Image credit: Bacon Cph, CC BY 2.5, via Wikimedia Commons)

In 2006, on the 150th anniversary of the discovery of Neanderthals, Professor Pabo announced that he would be working with the gene-sequencing company 454 to complete the Neanderthal genome Sequencing. 454 has developed a high-throughput sequencing technology that replicates tens of thousands of DNA fragments simultaneously for analysis.

The first challenge before them is getting enough samples. The bone fragments sent by the museum earlier brought some genetic information, but it was nowhere near enough to piece together a complete genome.

InAfter obtaining a new set of samples from Croatia, the researchers managed to obtain millions of base pairs of information, the first challenge was solved, but the second challenge came. Subsequent analysis found that these samples may be contaminated with modern human DNA, and the proportion from Neanderthals is pitiful, while DNA from contaminating microorganisms accounts for as much as 80%, indicating that most of the sequencing work Data is meaningless. Professor Pabo recalled that the experience at that time was disappointing.

During decades of exploration, Dr. Pabo and his team have steadily improved methods for isolating and analyzing DNA from ancient bone remains, finally making DNA sequencing extremely efficient. The seemingly impossible task was successfully tackled by Professor Pabo in 2010-they published the first Neanderthal genome sequence that year.

Rewriting textbook

In the course of their research, the team’s discoveries have rewritten textbooks. About two years after the project was launched, collaborators from Harvard Medical School discovered that Neanderthals had a genetic sequence similar to that of humans, which was not news. The problem is, they seem to be more like some humans. Specifically, Europeans and Asians appear to have more Neanderthal-like DNA in their bodies, and Africans have less.

Research people’s first reaction is to go wrong again. Because “Out of Africa Theory” was almost the only theory on the origin of human beings in the academic circle at that time, referring to the fact that modern humans came from a small group of ancient humans living in Africa. They walked out of Africa about 200,000 years ago and took root around the world. Depending on the distance, they arrived in the Middle East about 120,000 years ago, and Eurasia 50,000 years ago, where they encountered Neanderthals living in Europe and replaced them.

▲Dr. Pabo’s findings are significant, revealing the distribution of human populations on Earth as Homo sapiens moved out of Africa and around the globe. Neanderthals lived in western Eurasia, while Denisovans lived in the east. When our ancestors came to these areas, they also mated with them, leaving permanent traces in our DNA (Image source: Reference [2])

After ruling out the possibility of contamination, this finding by Professor Pabo’s team suggests that the process by which homo sapiens ancestors replaced Neanderthals was complex and lengthy. They did not simply exterminate the latter, but mated with Neanderthals and gave birth to children. These children are numerous, and they also form families, have children, have more offspring, and eventually grow and multiply in Europe, Asia, and the Americas.

To this day, modern humans living in Eurasia still contain about 1% to 4% of Neanderthal DNA, including Han Chinese.

What We Are

In an interview with the Nobel Prize Committee, Professor Pabo said the past 40,000 years were special because we were the only humans in the world during that time. If Neanderthals had survived to this day, how would we view them, or ourselves, differently?

Image source: Photo by The Royal Society, CC BY-SA3.0, Wikimedia Commons

We’ve had no chance to test the answer, but we know that the extinct Neanderthals left enough influence on the health of modern humans to make us aware of ourselves Not that special. Some studies have shown that Neanderthals left us with little but enough DNA to alter the functioning of the immune system, or the patterns of sleep, or the management of our emotions. In the words of Professor Pabo’s interview, they do affect our physiology (see WuXi AppTec’s content team in today’s next article).

Professor Pabo also wondered if there were any mutations brought about by Neanderthals that made modern humans more fearless and more exploratory. In the “New Yorker” report, he asked, what made ancient humans decide to set off towards the endless sea with their humble ships? How many people have been buried in the waves before finally reaching those small islands in the Pacific Ocean? What is the purpose of this kind of courage to set off rashly without knowing what to do next?

The answer may or may not be in the genes that Neanderthals left us, but that doesn’t matter anymore. We only know that human beings require not only intelligence beyond all species, but also a little bit of madness to make us so different on this planet. Professor Pabo’s work gives us an opportunity to examine this.


[1] Sleeping with the Enemy, Retrieved October 3rd, 2022, from https:https://www.newyorker.com/magazine/2011/08/15/sleeping-with-the -enemy

[2] The Nobel Prize in Physiology or Medicine 2022, Retrieved October 3, 2022, from https://www.nobelprize.org/uploads/2022/10/press-medicine2022.pdf

[3] Ancient DNA pioneer Svante Pääbo wins Nobel Prize in Physiology or Medicine, Retrieved October 3rd, 2022, from https:https://www.science.org/content/article/nobel -prize-physiology-or-medicine-2022

[4] How Neanderthal DNA affects human health – including the risk of getting Covid-19, Retrieved October 3rd, 2022, from https:https://www.cnn.com/2020/ 12/09/health/neanderthal-genes-human-health-covid19-scn-wellness/index.html

[5] Nobel Prize in Physiology or Medicine Is Awarded to Svante Pääbo, Retrieved October 3rd, 2022, from https:https://www.nytimes.com/2022/10/03/ health/nobel-prize-medicine-physiology-winner.html

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