Fu Qiaomei was his former doctoral student and is now the director of the Archaeological DNA Laboratory of the Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences. When the China Science Daily contacted her, the congratulations she wrote to her

text | Intern reporters of "China Science Daily" Tian Ruiying Meng Lingxiao Reporter Hu Minqi

"This year's first Nobel Prize was a big upset!"

On October 3, the 2022 Nobel Prize in Physiology or Medicine was announced. Swedish scientist Svante Pääbo (Svante Pääbo) won the award for his "discovery in the extinct ancient human genome and human evolution ". Many followers called it "unpopular".

persistence is the biggest evaluation of Fu Qiaomei . Fu Qiaomei is his former doctoral student and is now the director of the Archaeological DNA Laboratory of the Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences. When " China Science Daily " contacted her, the congratulations email she wrote to her supervisor had not had time to send.

22 Nobel Prize winner in Physiology or Medicine Svante Pääbo Picture source: Nobel Prize Committee official website

Related reading | Just now, the 2022 Nobel Prize in Physiology or Medicine was announced!

"China Science Daily": What kind of person do you know of Nobel Prize winners?

Fu Qiaomei: He is very persistent and has a very clear interest orientation. Since 1997, he has been the director of the MaxPu Institute of Evolutionary Anthropology. Paleogenetics can be said to be pioneered by him from scratch, and he has been conducting this research firmly.

"China Science Daily": Why did this research win the Nobel Prize?

Fu Qiaomei: After nearly ten years of development, research in the field of paleogenomics has had a great radiation impact. In addition to the genome itself, it also has a profound impact on us modern people, such as functional genes, and solving other unsolved mysteries of humanity.

In addition, paleogenomics has also affected research in other fields, including humans, animals and pathogens, which can be said to have radiated to various fields.

"China Science Daily": What qualities or habits have a profound impact on your scientific research?

Fu Qiaomei: His persistence has greatly affected me, especially when I discovered important research. His first reaction was never to be happy, but to think about whether the result is reliable, and to verify it in various ways, and to prove whether the discovery is wrong and whether there is a problem. This is a great wake-up call for us.

he, why do you reshape Neanderthal history

Have worked for a day very tired, but the 5-year-old son is just the time to make a fuss. After the child fell asleep, a crazy question trapped him: if everyone today has 1% to 4% Neanderthal genes, then the random combination of DNA fragments may produce a strange result - a child is completely Neanderthal from birth, and this child happens to be his unruly son?

Parbo calculated the probability of this matter especially carefully, and the result was that the number was a zero and 76,000 zeros after the decimal point, plus some numbers. In other words, it is not possible for a real Neanderthal to come into the laboratory to provide him with blood samples in the future, and it does not exist!

This is what Phabo described in his book. He is so cute that he is foul.

If there is a person's name bound to ancient DNA, it is Svanter Parbo.

Parbo is a Swedish evolutionary geneticist and the director of the Institute of Evolutionary Anthropology of the Max Planck Society in Germany.

From the first to secretly test the millennium mummy DNA in his student days to the first time in history to the first time he drew a Neanderthal genome map. It took him 30 years to push his scientific research career to the extreme.

Every outstanding scientist carries a history of science

In the 1980s, what choice would a doctorate who had not yet "departed" have made when facing two completely different career paths? One is the mainstream promising molecular biology , and the other is the mysterious but difficult to see the future of Egyptian ancient relics.

Pab did not follow the advice of most of his companions to choose the former, but chose the ancient history that he had been obsessed with since the age of 13, and then embarked on his own path - bringing archaeology into the molecular era.

led him by the famous evolutionary biologist Alan Wilson, the inventor of polymerase chain reaction (PCR), and later the winner of Nobel Prize in Chemistry .

In Parbo's subsequent research career, three articles established his position in the academic field.

In 1984, Pabo quietly became the first person in the world to extract DNA from a mummy that had been dead for more than two thousand years. A year later, his paper "Molecular Cloning of Ancient Egyptian Mummy DNA" appeared on the cover of " Nature ", causing a sensation in the academic community. Importantly, his extraordinary passion for unorthodox thinking and projects made him destined to be a unique pioneer.

12, Pabo extracted mitochondrial DNA 3 from the extinct ancient human, the Neanderthal for the first time in the interdisciplinary laboratory he created and successfully sequenced it. His team reported Neanderthal sequencing results in the journal " cell ", providing ironclad evidence for Alan Wilson's modern human origin theory of "going out of Africa".

And in 2010, the Neanderthal genome sketch was completed, and the story about human origin took a dramatic turn. Parbo and his 50 scientists worked together in Science revealed that today, everyone except Africa carries the Neanderthal genetic code , and this ancient human has never disappeared!

Parbo, who loves skiing in the Alps, once said that what is more spectacular than the steep snow scene around it is their paper describing Neanderthal DNA sequences. That is the heavenly book of life.

If the field of ancient DNA research is compared to the Alpine mountains, then in the eyes of latecomers, Pabo is undoubtedly the person who reached the top of Mont Blanc in this era.

When it comes to scientific research, he did not let

In 1987, the polymerase chain reaction (PCR) technology to amplify specific DNA fragments emerged, which made it possible to amplify trace DNA in ancient materials, but this technology challenges researchers to a huge challenge. The storage conditions of old samples are not favorable, and the available DNA is very limited, or even no, which is difficult to achieve even through PCR. Therefore, it is very important to systematically establish a reliable DNA amplification process from a scientific point of view.

But Pabo quickly realized that modern exogenous DNA pollution experiments are a serious problem. It even caused a trough period for more than a decade in the field of ancient DNA research.

The so-called exogenous DNA pollution refers to the possibility that anyone who has been exposed to ancient specimens, detection instruments, or even DNA fragments in the environment may enter the sample and be regarded as residual ancient DNA, thus destroying the entire experiment.

In 1990, the first thing Pabo did when he came to University of Munich to start his independent scientific research career was to "inject a new rigorous look into human history research."

He used almost crazy paranoia to build the world's first clean room for ancient DNA research. He formulated "reliability criteria" for experiments and a series of iron laws of work. Those steps require ritual content that looks like sacred and cannot be desecrated at all.

team tried their best to be meticulous, and Pabo was still worried about pollution at night. Even though he was so pious, they still returned in vain time and time again.

However, just as the Pabo team worked hard to develop methods to detect and eliminate pollution, he found that Nature and Science published a series of flashy papers, rushing to find super ancient DNA, which was simply a fantasy under the technical conditions at that time. The pitiful DNA sequence that the team has obtained through hardships for tens of thousands of years is not worth mentioning in front of those articles.

He has seen more than once that advancement in science is a painful process, and “it takes a long time to convince your closest partners and most people around the world to think about new ideas.”

As a student of Pabo, adhere to the rigorous and fact-oriented style, which also had an important impact on Fu Qiaomei, director of the Archaeological DNA Laboratory of the Institute of Vertebral Paleontology, the Chinese Academy of Sciences, to establish a scientific research attitude.

She said: "Whenever I get a result that may change my previous understanding, my first reaction is often 'Did I make any mistakes?', worried that the sample will be contaminated or the analysis method will be wrong, and then I keep finding faults and arguments. All the methods of finding faults have been tried, and after I am sure, I can relax happily."

Capriciousness of scientific development

In the late 1990s, with the Pabo team successfully extracting and sequencing Neanderthal mitochondrial DNA, the hypothesis of "mitochondrial Eve" was confirmed, supporting all modern people who evolved from Homo sapiens , which came out of Africa, instead of originating in many places. But in fact, the confrontation about human origin patterns has not diminished because this evidence is incomplete. The limitation of

mitochondrial DNA is that it can only inherit through maternal lineage. To find the accurate relationship between modern humans and Neanderthals, nuclear DNA must be relied on. However, in the extract, the amount of nuclear DNA is only 1/1000 to 1/100 of the mitochondrial DNA, unless there is huge progress in amplification technology.

Before this, the Parbo team could only work hard to improve the extraction technology while praying that the lab members could live long enough.

In early 2000, the "second generation sequencing method" was born, and it was hoped to fundamentally change ancient DNA and many other biological research. Parbo then decided to officially launch the Neanderthal Genome Project at the Institute of Evolutionary Anthropology, which he founded by the Max Planck Society in Germany.

But this plan quickly encountered a bottleneck. Although the second-generation sequencing method at that time improved the efficiency of obtaining DNA sequences, it still needed to be based on enough bone samples.

How to obtain precious specimens from Eastern European countries back then is a contest outside of science, but for Parbo, he doesn't even know who the opponent is. The most disappointing thing is that he devoted all his connections and all his mediation capabilities, and the bones he obtained could not support him in completing the sequencing work.

At that moment, all efforts went into nothing. They have no choice but to wait for the next major technological innovation. But only Pabo believes that that is not their limit.

He remembered the military training he had received in Sweden when he was young, including interrogation training for war criminals. One of the methods was to ask the same question repeatedly over and over again. He used this almost "cruel" method to force his team that the extraction and amplification technology could not be broken through. The only way was to reduce DNA losses during the experiment. Ultimately, they identified and improved the steps that caused DNA loss, which was a tangible improvement to reverse the world.

But the good times didn't last long. What made Pabo fall into despair again was that their experimental results were questioned by foreign DNA pollution...

This not only has the limitations of human beings' exploration of unknowns, but also, as Pabo revealed, "Scientific research is a social work, and the dogma advocated by high-powered people and influential scholars often determines the 'common sense' of science", which will hinder more scientists from pursuing the truth objectively and impartially.

But at the same time, this process also makes people see that only an inclusive, open and cooperative mentality can condense the team into the ultimate force to break through the haze when the crisis of scientific research is shrouded in.

Reference Books: Svanter Parbo "Neanderthals"