Inheritance Center｜Ode to courage: One article understands the 2022 Nobel Prize in Physiology or Medicine
Financial Street Telecommunications/ Nobel Prize in 022-10-05 08:00
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Financial Street Telecommunication Monday Nobel Prize The origin of human beings has always been a topic of interest to people. Where do we come from? What does modern people have to do with our predecessors? What sets Homo sapiens apart from other races? Swedish Swedish scientist Swant Parbo , who won the 2022 Nobel Prize in Physiology or Medicine, completed a seemingly impossible thing through his pioneering research: sequencing the genome of Neanderthal . Neanderthals are extinct relatives of modern people.
On the afternoon of October 3, the 022 Nobel Prize in Physiology or Medicine was awarded to Professor Svante Pääbo for his outstanding contributions in the field of paleogenomics. Many people say that this year's Nobel Prize is a bit unpopular, , but as long as you understand Professor Pabo's work, you will know that his research is of great significance to human understanding itself and is closely related to the health of modern humans. In today's article, WuXi AppTec content team will come to the new Nobel Prize winner with everyone to learn about his life and research.
▲Dr. Svante Pääbo, who won the Nobel Prize this year,
(Picture source: Reference [2])
"Nobel Second Generation"
It is difficult to reconcile with his father
Professor Pabo works at the Max Planck Institute in Germany. October 3 is the local holiday to commemorate the unity of the two Germanys. When he finished his last sip of tea and wanted to go to his mother-in-law's house to pick up his daughter, a phone call from Sweden came over. For a moment, he thought something was wrong with his vacation hut in Sweden, such as lawn mower broken. He was surprised after receiving the news of the award. In the subsequent interview, he admitted that although he won many awards, he never thought that his work on genomics in ancient humans would still be the Nobel Prize.
▲The official account of Nobel Prize said that when he learned the news of the award, Professor Pabo was drinking coffee (Professor Pabo changed to drink tea in an interview) (Picture source: Nobel Prize official Twitter; Credit: Linda Vigilant)
Phabo grew up in Stockholm . When reading the list, the Nobel Prize Committee also proudly said that this year we welcomed a Swedish winner. His mother is a refugee from Estonia and has a great love for science. She once conducted research on the research team of a biochemist named Sune Bergström, who, although she had her own independent family, became Parbo's biological father in an extramarital affair. In 1982, Bergström shared the Nobel Prize in Physiology or Medicine for discovering the physiological effects of prostaglandins and similar hormones. From this point of view, Parbo can be said to be the "No Generation II".
A 2011 report by The New Yorker mentioned that Bergström takes the young Parbo for a walk every Saturday in the name of work, in the name of his young Parbo, where he doesn't have to worry about being recognized. His wife also tacitly never calls him during Saturday "working hours", hoping to keep the secret sealed forever. It was not until shortly before Bergström's death that his son learned of Parbo, a half-brother.
▲The father, who is also the Nobel Prize winner, did not have the greatest impact on Parbo as he imagined (Image source: Sune K. Bergström – Facts. NobelPrize.org. Nobel Prize Outreach AB 2022. Mon. 3 Oct 2022. https://www.nobelprize.org/prizes/medicine/1982/bergstrom/facts/)
Nobel Prize Committee interview joked about Pabo's Nobel Prize blood relationship and asked if he had any different feelings as a Nobel Prize second-generation winner. Parbo was silent for a few seconds after hearing the question, sighed, and then hesitantly suggested that his father had not had that much influence on him. In fact, he regrets that his mother failed to witness the arrival of this day because it was she who inspired her growth on the path of science.
fascinated by history
Since I was very young, Pabo has been interested in things with a sense of history. In the dense forests of Sweden, he can sometimes find some broken pottery pieces left by prehistoric human and use them to decorate his room. Once, his mother took him to Egypt for a trip. After seeing the pyramid, the young Parbo was even more fascinated by it. When he was in college, he was determined to become an Egyptologist.
But the university courses were a little different from what he imagined. Originally, he wanted to study mummies, but the course only arranged to analyze hieroglyphs. Bored about this, Pabo decided to switch to medicine and cell biology , but he never forgot his love for mummies. His doctorate degree is related to virus research, but he secretly studied the method of extracting DNA from ancient mummies without telling his tutor.
Because he was afraid that his mentor would think he was not doing his job properly, even if the DNA was successfully extracted from a mummified child, he would only dare to vote for an unknown little magazine to avoid causing trouble. But this paper that I tinkered with in my spare time is of extremely high quality. 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 mistakenly thought that Parbo was a young professor and wrote back to him to ask if he could come to his laboratory for a visit. Pabo had no choice but to reply and said that he not only did not have a laboratory, but he had not even obtained a doctorate degree.
Image source: 123RF
Finally, after Parbo's paper was sorted into English, was published in the magazine " Nature " in the form of a cover article and was reported by Time magazine, believing that this is "one of the greatest achievements made in recent use of molecular biology ." Pabo's colleagues in Sweden disagreed with this and urged him not to waste time on the strange hobbies of mummies and to come back quickly to continue studying the virus.
Parbo did not hesitate much, left Sweden and went to California and joined Professor Wilson's lab. They had the same interest in ancient DNA.
Impossible task
In the official press release of the Nobel Prize, Professor Pabo's genetic sequencing work on ancient humans was called "impossible task". This is because the natural chemical properties of DNA determine that it is easily degraded, and it will also be contaminated by DNA from modern humans and even bacteria. I want to find very few ancient human samples, extract the few DNA left from it, and remove pollution and analyze it accurately. It sounds unlikely.
▲DNA is located in two different locations in the cell: nucleus DNA contains most of the genetic information, and the remaining small part is located in mitochondrial . After ancient humans died, DNA would degrade over time and be contaminated by DNA from bacteria and contemporary humans (Image source: Reference [1])
This is the huge challenge that Parbo encountered when he first arrived in California. The DNA of ancient Egyptians is very similar to that of modern people, and some fragments are exactly the same.How do we make a distinction? In order to make a technical breakthrough, he chose to practice with DNA from extinct animals, as far as big sloth and mammoth that disappeared tens of thousands of years ago, and to Tasmanian tiger that have only been extinct for decades. In the process of these explorations, Professor Pabo has opened up a new field of paleogenomics.
The colleagues he worked with had a very high evaluation of him, saying that he turned science fiction like Jurassic Park into real science, . Without Professor Paleo, paleogenomics would not exist. What is rare is that Professor Pabo also maintained enough modesty, saying that this is the contribution of the team, not only him.
A few years later, Professor Pabo received a call from the Rhine State Museum in Germany, asking him if it is possible to extract useful DNA from some ancient samples. He replied that unless the sample can be dissolved and analyzed, it is impossible to know whether the sample is still intact, and the probability of success is only 5%.
A few months later, he received a small piece of humerus from ancient humans, which was the Neanderthals who later became famous.
Neanderthal
The original Neanderthal sample was found in a limestone cave in Germany. was not valued earlier and was once treated as garbage, and its completeness was almost certainly greatly reduced. A local businessman rescued the remaining bone pieces and handed them over to a fossil collector, who saw the shadow of humanity. At that time, shortly after Darwin published " Species Origin ", these broken bone fragments also triggered the protracted debate on the origin of humans in .
Later, people found more and more complete Neanderthal skeletons. Although their bones are thicker and the shape of the skulls looks strange, the anatomy families still see too many similarities to the human skeleton. believes that if Neanderthals lived until now and walked into the subway in New York City, people around them would not pay much attention to him.
▲Neanderthals are very similar to modern humans (Photo source: Bacon Cph, CC BY 2.5 https://creativecommons.org/licenses/by/2.5, via Wikimedia Commons)
006, on the occasion of the 150th anniversary of the discovery of Neanderthals, Professor Pabo announced that he would cooperate with the gene sequencing company "454" to complete the sequencing of the Neanderthal genome. 454 Company has developed a high-throughput sequencing technology that can replicate tens of thousands of DNA fragments for analysis at the same time.
The first challenge before them is to get enough samples. Although the bone fragments sent by the museum earlier brought some genetic information, they were far from enough to piece together the complete genome.
After obtaining a new set of samples from Croatia , the researchers successfully obtained millions of base pairs of information. The first challenge was considered to be solved, but the second challenge came immediately. subsequent analysis found that these samples may be contaminated by modern human DNA, and the proportion from Neanderthals is pitifully small. DNA from contaminated microorganisms accounts for as much as 80%, indicating that most of the data in the sequencing work is meaningless. Professor Pabo recalled that the experience at that time was desperate.
During decades of exploration, Dr. Pabo and his team have steadily improved the methods of isolating and analyzing DNA from the remains of ancient bones, finally making DNA sequencing very efficient. The seemingly impossible task was successfully overcome by Professor Pabo in 2010 - that year, they published the first Neanderthal genome sequence.
rewrite textbook
The first reaction of people to study is that another error occurred. Because "theory of leaving Africa" was almost the only theory about the origin of human beings in the academic circle at that time, it means that modern people all 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 at Middle East about 120,000 years ago, and arrived at Eurasian 50,000 years ago, and met Neanderthals living in Europe and replaced them.
▲Dr. Pabo's discovery is of great significance. It reveals the population distribution on the earth when Homo sapiens walked out of Africa and came to all parts of the world. Neanderthals live in the west of Eurasia, while Denisovans live in the east. When our ancestors came to these areas, they also had mating with them, leaving eternal traces in our DNA (Image source: Reference [2])
After eliminating the possibility of pollution, this discovery by Professor Pabo's team showed that the process of replacing Neanderthals by Homo sapiens ancestors was complicated and long. They did not simply drive the latter away, but had mate with the Neanderthals and gave birth to children. There are not many of these children, and they will also form families, have children, give birth to more offspring, and eventually grow and reproduce in Europe, Asia and America.
To this day, modern humans living in Eurasia still contain about 1% to 4% of Neanderthal DNA, including Han people.
Why do we be human
In an interview with the Nobel Prize Committee, Professor Pabo said that the past 40,000 years are very special because we are the only humans who exist in this world during this period of time. If Neanderthals can live to this day, what will be different in our view of them or our own?
Image source: Photo by The Royal Society, CC BY-SA3.0, Wikimedia Commons
We no longer have the chance to test the answers to the questions, but we know that the extinct Neanderthals have left a big enough impact on the health of modern people to make us realize that we are not that special. Some studies show that although Neanderthals don’t have much DNA left to us, it is enough to change the function of the immune system, or sleep patterns, or mood management. In the words of Professor Pabo’s interview, they do affect our physiology (see the report of the WuXi AppTec content team today for details).
Professor Pabo also thought about whether there are any mutations brought by Neanderthals that make modern people more fearless and more exploratory. He asked in the report of "The New Yorker", what made ancient humans decide to set out towards the endless sea with their simple ships? How many people were buried among the waves before finally reaching those small islands in the Pacific? What is the purpose of this courage to set out rashly without knowing the future?
The answer may be hidden in the genes left to us by the Neanderthals, or maybe not, but this is no longer important. We only know that the reason why people not only need wisdom beyond all species, but also a little bit of madness to make us look so unique on this planet. Professor Pabo’s work gives us the opportunity to look at this.
Reference:
[1] Sleeping with the Enemy, Retrieved October 3rd, 2022, from 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 piloter Svante Pääbo wins Nobel Prize in Physiology or Medicine, Retrieved October 3rd, 2022, from 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://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://www.nytimes.com/2022/10/03/health/nobel-prize-medicine-physiology-winner.html
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