2022 Nobel Prize in Biomedicine is unexpected, human evolutionary genetics wins the prize for the first time

At 11:30 a.m. local time on October 3, 2022 (17:30 p.m. Beijing time on October 3), the Nobel Prize Committee announced that the 2022 Prize in Physiology or Medicine will be awarded to Swedish biologist and evolutionary geneticist Svante Pääbo in recognition of his discovery of genomes related to extinct ancient humans and human evolution.

Svante Pääbo (1955-)

Svante Pääbo was born on April 20, 1955 in Stockholm, Sweden, the son of Estonian chemist Karin Pääbo and biochemist Sune Bergström, who shared the 1982 Nobel Prize in Physiology or Medicine with Bengt I. Samuelsson and John R. Vane. Svante Pääbo received his PhD from Uppsala University in 1986, studying how the E19 protein of adenovirus regulates the immune system.

Wang Chuanchao, a professor at Xiamen University, told Fanpu that since Svante Pääbo started ancient DNA research in the 1980s, he has been working hard to explore ancient DNA experimental techniques and establish ancient DNA research standards. With the continuous emergence of amplification and sequencing technologies such as molecular cloning, PCR, second-generation sequencing technology, primer extension capture and liquid phase hybridization capture, ancient DNA research has gradually become a widely used and promising field. Ancient DNA research provides a very valuable reference for the origin and evolutionary history of mankind. In 2010, a research team led by Svante Pääbo of the Max Planck Institute in Germany sequenced the whole genome of the extinct Neanderthal and found that there was no Neanderthal genetic component in modern Africans, but there was 1% to 4% Neanderthal admixture in modern populations outside of Africa. Subsequently, the whole genome of the Denisovans who lived in North Asia 40,000 years ago was also successfully analyzed, and the human origin model was revised to "recent African origin with hybridization."

Today’s article is excerpted from Svante Pääbo’s popular science book “Neanderthals”, which tells the history of the development of paleogenetic research from a first-person perspective.

Author | Svante Pääbo

Translator | Xia Zhi

Proofread by Yang Huanming

I didn’t start out studying Neanderthals, I started out studying ancient Egyptian mummies. My mother took me to Egypt when I was 13, and I’ve been fascinated by its ancient history ever since. But as I began to do this research in earnest at Uppsala University, it became increasingly clear that my fascination with pharaohs, pyramids, and mummies was just a romantic dream of adolescence. I did my homework, memorized hieroglyphics and historical facts, and even spent two consecutive summers at the Mediterranean Museum in Stockholm cataloguing pottery and other artifacts. I might have become an Egyptologist in Sweden, working at the same museum. But I noticed that the same people were doing much the same things the second summer as the first. Moreover, they were eating the same meals at the same restaurants at the same times, discussing the same ancient Egyptian mysteries and academic gossip. In fact, I began to realize that Egyptology as a field was moving too slowly for me. It wasn’t the kind of professional life I wanted. I wanted to experience more excitement, to have more connections with the world I saw around me.

This awakening threw me into a crisis of sorts. My father had been a doctor who became a biochemist. Inspired by his father, I decided to study medicine and then basic research. So I entered the medical school at Uppsala University and was surprised after a few years to find that I really enjoyed seeing patients. Being a doctor seemed to be one of the few professions where you could not only meet a wide variety of people, but also have an active influence on their lives. And the ability to communicate with people and build relationships was a talent I had not expected to have. After four years of medical research, I faced another small crisis: should I become a doctor or switch to the basic research I had originally planned to do? I chose the latter, thinking that after getting my doctorate I could (most likely) return to the hospital. I joined the laboratory of Per Pettersson, who was one of the most sought-after scientists in Uppsala at the time. Not long ago, his research group had cloned the gene sequence for an important class of transplantation antigens for the first time. These protein molecules are located on the surface of immune cells and mediate the recognition of viral and bacterial proteins. Not only has Patterson produced exciting biological insights relevant to clinical practice, his laboratory is one of the few in Uppsala to have mastered new methods for manipulating DNA cloning by introducing bacteria.

Patterson invited me to join a team studying a protein encoded by an adenovirus. Adenovirus is a virus that causes diarrhea, cold-like symptoms, and other annoying symptoms. The viral protein was thought to bind to transplant antigens inside cells so that once it was transported to the cell surface, it would be recognized by immune system cells and then activate the immune system to kill other infected cells in the body. Over the next three years, I and others studied this protein and began to realize that our view of the protein was completely wrong. We found that the viral protein was not an unlucky target for the immune system to attack, but instead it sought out transplant antigens inside cells, bound to them, and prevented them from being transported to the cell surface. Since the infected cell had no transplant antigens on its surface, the immune system could not recognize that it was infected. In other words, the protein shielded the adenovirus. In fact, it allowed the adenovirus inside the cell to survive for quite a long time, perhaps even as long as the person it infected. The discovery that the virus could shield itself from the host's immune system in this way was truly unexpected. We ended up publishing our work in several high-profile papers in top journals. In fact, many subsequent studies have shown that other viruses use similar mechanisms to evade the immune system.

It was my first taste of what it was like to work on cutting-edge science, and it was fascinating. It was also my first (but not the last) experience of seeing that scientific progress is often a painful process: learning that you and your peers are wrong, and convincing your closest associates and much of the world to consider new ideas takes even longer.

But somehow, in the midst of my excitement about biology, I could not quite shake off my fascination with ancient Egypt. Whenever I could, I attended classes at the Institute of Egyptology. I always took classes in Coptic, the language spoken by the ancient Egyptian pharaohs. I became friends with Rostislav Holthoer, a cheerful Finnish Egyptologist with strong social, political, and cultural connections. In the late 1970s and early 1980s, I often spent long evenings at Rostislav's home in Uppsala, over dinner. I often complained that although I loved Egyptology, it was hard to see the future. I also loved molecular biology, which could continue to improve human welfare. I had to choose between two equally attractive career paths - it was too painful. Of course, this did not seem sympathetic, because this young man did not know how to make a decision, but both options were excellent.

But Rostislav was patient with me, and he kept listening. I explained how scientists can now extract DNA from any organism (it could be a fungus, a virus, a plant, an animal, or a human), insert it into a plasmid (a DNA carrier molecule that comes from a bacterial virus), and introduce the plasmid into bacteria, which, together with the bacterial host, will make hundreds or thousands of copies of the foreign DNA. I also explained how to determine the four nucleotide sequences of a foreign gene and how to find differences between the DNA sequences of two individuals or two species. The more similar two sequences are (that is, the fewer differences there are between them), the more closely they are related. In fact, the number of shared mutations can be used to infer not only how a particular sequence evolved from a common ancestral DNA sequence over thousands and millions of years, but also the approximate age of those ancestral DNA sequences. For example, in a 1981 study, British molecular biologist Alec Jeffreys analyzed the DNA sequences of a hemoglobin protein gene in the blood of humans and apes and inferred when the gene began to evolve independently in humans and apes. I explained that this method could soon be applied to many genes, many individuals in any species. This allows scientists to determine how different species were related in the past and when they began their own evolution, a method that is more reliable than morphology or fossil studies.

As I explained all this to Rostislav, a question began to dawn on me: Can this method only be used to sequence DNA from blood or tissue samples of living humans and animals? Can this method be used to sequence DNA from Egyptian mummies? Can DNA molecules survive in mummies? Can they also insert into plasmids and replicate in bacteria? Is it possible to study ancient DNA sequences to shed light on how ancient Egyptians were related to each other and to people today? If so, we could answer questions that conventional methods of Egyptology cannot. For example, how are Egyptians today related to those who lived during the reign of the pharaohs, about 5,000 to 2,000 years ago? Was there a massive population replacement in Egypt due to major political and cultural changes, such as the conquests of Alexander the Great in the 4th century BC and the Arab invasions in the 7th century? Or did these military and political events simply lead to the adoption of a new language, a new religion, and a new way of life? Are the people living in Egypt today, in general, the same people who built the pyramids? Or did their ancestors mix with the invaders, so that the Egyptians today are completely different from the ancient Egyptians? Questions like these are exciting. Of course, others must have thought of them too.

I went to the university library and looked up relevant journals and books, but I didn't find any reports of getting DNA from ancient materials. It seemed that no one had ever tried to get ancient DNA; or if they had, they hadn't succeeded, because if they had, they would have certainly published their findings. I discussed this with the more experienced graduate students and postdocs in Patterson's lab. They said, given the sensitivity of DNA, why do you think it can be preserved for thousands of years? Our conversation was frustrating, but I didn't give up hope. When I searched the literature, I found several articles where the authors claimed that they had detected proteins from animal skins that were hundreds of years old in museums - proteins that could still be detected by antibodies. I also found studies claiming to have found cell outlines in ancient Egyptian mummies under a microscope. So something was indeed preserved. I decided to conduct experiments.

The first question was whether DNA could survive long-term in tissue after death. I speculated that if tissues were dried, as in the mummies of ancient Egyptian embalmers, then DNA might survive long-term, since enzymes that degrade DNA need water to activate. This was the first thing I needed to test. In the summer of 1981, when the lab was quiet, I went to the supermarket and bought a piece of calf's liver. I taped the store receipt to the front page of a brand-new lab notebook in which I would record these experiments. I labeled the notebook with my name, if for no other reason than that I wanted to keep my experiments as secret as possible. If Patterson thought these experiments were unnecessary and found them distracting, he might forbid me to do them. After all, the molecular mechanisms of the immune system were a hotly contested field, and I should devote my full attention to it. In any case, I wanted to keep everything secret to avoid being ridiculed by my colleagues if I failed.

To mimic the ancient Egyptian mummies, I decided to seal the liver in the oven in the lab and heat it to 50 degrees Celsius to mummify it. The first consequence of this was that my secret project would be made public. The next day, the strange smell attracted a lot of gossip, and I had to make my project public before everyone found and disposed of the liver. Fortunately, as the dehydration process progressed, the smell was no longer strong, so no rotten smell or complaints were passed to the professor.

After a few days, the liver became hard, dry, and dark brown, like an Egyptian mummy. I began to extract DNA from it, with great success. The DNA I obtained was short fragments of only a few hundred nucleotides, not thousands like DNA extracted from fresh tissue, but still enough for experiments. My idea was confirmed. It was not ridiculous to think that DNA could survive in a dead tissue for at least a few days or weeks. But what about thousands of years? The obvious next step was to try the same method on Egyptian mummies. This is where my friendship with Rostislav came in handy.

Rostislav knew about my struggles with Egyptology and molecular biology and was happy to support my attempts to bring Egyptology into the molecular age. He was the director of a small university museum that housed some mummies. He agreed to my request to sample the mummies, though he would not allow me to cut them open and take their livers. But if the mummy had been torn open and its limbs were broken, Rostislav allowed me to take a small piece of skin or muscle tissue from the broken mummy for DNA extraction. There were three such mummies available. When I put the scalpel to the skin and muscle of a person who had lived 3,000 years ago, I found that the texture of the tissue was different from the calf liver in my oven. The calf liver was hard and easy to cut. But the mummy was brittle and the tissue broke into a brown powder when cut. I used the same process for extracting the mummy as the liver. The mummy extract was different from the liver extract. The former was brown like the mummy, while the latter was clear as water. I applied an electric field to migrate the mummy extract through the gel to extract the DNA, and then stained it with a dye. If the dye binds to the DNA, it will fluoresce pink under the UV light. But I saw nothing but brown stuff. In fact, it did fluoresce under the UV light, but it was blue instead of pink, so it was not the DNA we expected. I repeated the process on two other mummy samples. Again, no DNA. All the extracts I expected to contain DNA turned out to be just unidentified brown stuff. My lab colleagues seemed to be right: even inside cells, fragile DNA molecules need to be constantly repaired to stay intact. How could they survive for thousands of years?

I put my secret lab notebook in the bottom of my desk drawer and went back to studying viruses that cleverly trick the immune system with little proteins, but I couldn't get the mummies out of my mind. How could anyone see remnants of cells in a mummy? Maybe the brown stuff was actually DNA that had undergone some chemical modification so that it looked brown and fluoresced blue under ultraviolet light. Maybe it was naive to expect DNA to be present in every mummy. Maybe it would take analyzing many mummies to find a good enough sample. The only way to find out was to convince museum curators to sacrifice many mummies, perhaps in vain, in the distant hope that one of them would yield ancient DNA. I didn't know how to get their support. It seemed that I needed a quick, low-loss method to analyze many mummies. My medical training gave me a clue. For example, using a biopsy needle to remove a tiny piece of tissue from a suspected tumor, fixing and staining it, and then looking at it under a microscope. The recognizable details are usually obvious, allowing a trained pathologist to distinguish between normal cells in the intestinal mucosa, prostate or breast, and cells that are beginning to change, thereby detecting early tumors. In addition, researchers can use specific DNA dyes in microscope slides to test for the presence of DNA. All I need to do is collect a small sample from a large number of mummies, then perform DNA staining and microscopic observation. Obviously, if you want to get a large number of mummies, you have to start with the largest museums. But an over-excited student from Sweden who wants to get even a little tissue for a whimsical project will undoubtedly arouse the suspicion of the curator.

Rostislav was still sympathetic. He told me that there was a large museum with a large collection of mummies that might be willing to cooperate. It was the Staatliche Museen zu Berlin. This complex of museums was located in Berlin (East Berlin), the capital of the then German Democratic Republic. Rostislav had spent several weeks there studying the ancient Egyptian pottery collection. He had obtained permission to work in the museum as a Swedish professor. However, his ability to become close friends with several of the museum staff members was mainly due to his ability to develop deep cross-border friendships. In the summer of 1983, I took a train to the ferry in southern Sweden and arrived in the GDR the next morning.

I stayed in Berlin for two weeks. Every morning, I had to pass several checkpoints to enter the storage room of the Bode Museum, one of the national museums. The Bode Museum is located on an island in the Spree River near the center of Berlin. It has been nearly 40 years since World War II, but the museum still clearly retains traces of the war. I saw bullet holes on the walls around the windows, which were left by the Soviet army's machine gun fire when it captured Berlin. On the first day, they took me to visit the pre-war ancient Egyptian artifacts exhibition and gave me a construction worker's hard hat. I soon understood why. The roof of the exhibition hall had huge holes left by artillery and bombs. Birds flew in and out, and some even built nests in the pharaoh's sarcophagus. All fragile artifacts have now been wisely stored elsewhere.

Over the next few days, the curator in charge of Egyptology showed me around the mummies. A few hours before lunch, I cut small pieces of tissue from the cracked and damaged mummies in his dusty, run-down office. Lunch was a bit of a hassle, as you had to go through all the security checks to get to a restaurant on the other side of the river. The food was greasy and washed down with lots of beer and schnapps. Back at the exhibition, we continued to drink schnapps throughout the afternoon. Although we spent hours discussing hypotheses about the future, I still managed to collect more than 30 mummy samples to take back to Sweden.

In Uppsala, I soaked the specimens in a salt solution to rehydrate them, then placed them on slides and stained them to observe the preservation of cells in the tissues. To prevent too many people from knowing what I was doing, I only worked on weekends and late at night. When I looked through the microscope, I was depressed by the appearance of the ancient tissues. I could hardly see fibers in the muscle samples, let alone any traces of cell nuclei that might contain DNA. I was almost desperate until one night I looked at a slice of cartilage from the outer ear of a mummy. Like cells in bone, cells in cartilage live in cavities in dense hard tissue. When I looked at the cartilage, I saw what seemed to be cell debris in the cavities. Excited, I stained the section with DNA. My hands were shaking as I put the slide under the microscope. There were indeed signs of DNA staining in the cartilage cells (see Figure 2.1). There was DNA in the cartilage!

With my spirits lifted, I continued to process all the other samples I had brought back from Berlin. Several looked promising. Of particular note was a piece of skin from the left calf of a child mummy, which had obvious cell nuclei. When I stained a piece of skin with DNA, the nuclei glowed. Since this DNA was in the nucleus, it could not have come from bacteria or fungi, even though it would appear randomly in tissues where bacteria or fungi were growing. This was definitive proof that the child's own DNA had been preserved. I took many microscope photos.

Figure 2.1 Microscopic image of cartilage tissue from an Egyptian mummy in Berlin. Some of the cell remnants between the cavities glow, indicating that DNA is likely to remain. Photo credit: Svante Pääbo, Uppsala University.

After staining the nuclei, I found DNA in three of the mummy samples. The child's sample had the most intact cells. But now another doubt began to invade me. How could I be sure that this was really an ancient mummy? Sometimes, in order to make a few dollars from tourists and collectors, scammers will pretend that recent bodies are ancient Egyptian mummies. Some of these mummies are later donated to museums. The staff at the Berlin Museum could not give me any records of the mummy's provenance, perhaps because the relevant records were destroyed in the war. Its age could only be determined by carbon dating. Fortunately, carbon dating expert Göran Possnert works at Uppsala University. He uses accelerators to determine the age of tiny ancient remains by measuring the ratio of carbon isotopes. I asked him how much it would cost to date the mummy, as I was worried that my meager student allowance would not be enough. He sympathized with me and promised that the dating would be free. He considerately mentioned the price. The real price was, of course, way beyond my means. I handed the small piece of mummy to Goran and waited for the results. For me, this is one of the most frustrating aspects of scientific research: when your work depends so much on other people, there is nothing you can do except wait for a phone call that may never come. But a few weeks later, I finally got the call I had been waiting for. The result was good news! The mummy was 2,400 years old. 2,400 years ago, around the time when Alexander the Great conquered Egypt. I breathed a sigh of relief, went out and bought a large box of chocolates to mail to Goran. Then I started thinking about publishing my discovery.

In the GDR I had learned that people living in the atmosphere of the time were very sensitive. I also knew that the museum director and other museum staff who would receive me would be disappointed by my perfunctory acknowledgments at the end of my paper. I wanted to handle this in a proper way, so I consulted with Rostislav and Stephan Grunert, a young but ambitious GDR Egyptologist whom I had met in East Berlin. Finally, I decided to publish my first article on mummy DNA in a GDR scientific journal. In my barely high school-level German, I wrote about my findings with difficulty, and attached photos of the mummies themselves and of DNA-stained tissues. At the same time, I also extracted DNA from the mummy. This time, I was able to prove that the extract contained DNA using a gel, and I attached a graph of the results of this experiment to my paper. Most of the DNA was degraded, but some fragments were still several thousand nucleotides long, about the same length as DNA extracted from fresh blood samples. This seemed to indicate, I wrote, that some ancient tissues might have DNA molecules large enough for us to study individual genes. I fantasized about what might be possible if the DNA of ancient Egyptian mummies could be systematically studied. At the end of my paper, I wrote hopefully: "The work of the next few years will show whether these dreams will come true." I sent the manuscript to Stefan, who corrected my German. In 1984, the paper was published in Das Altertum, a journal published by the Academy of Sciences of the GDR. But nothing happened. No one wrote to me, let alone asked for a copy. Although I was excited about my results, others did not seem to be so.

I realized that most people in the world were not in the habit of reading publications from the GDR. Later, I obtained similar results from a skull fragment of a mummified man, and in October of the same year, I submitted a paper based on these results to a seemingly suitable Western journal, the Journal of Archaeological Science. But to my dismay, the entire publication process was surprisingly slow, even slower than when I published my paper in the GDR. But when publishing a paper in a GDR journal, Stephen had to correct the language. I felt that this reflected that progress in the field of archaeology was as slow as the movement of a glacier. Finally, at the end of 1985, the Journal of Archaeology published my paper, but by then, the results in the paper had been overshadowed by other experiments.

Now that I had some mummy DNA in hand, the next step was clear: I needed to clone it in bacteria. I treated the DNA with an enzyme that allowed the ends of the DNA to bind to other DNA, then mixed it with a bacterial plasmid and added an enzyme that allowed the DNA fragments to join together. If all went well, I would have a hybrid molecule that was a combination of mummy DNA fragments and plasmid DNA. When I introduced these plasmids into bacteria, the hybrid not only replicated in large quantities in the bacterial cells, but also made the bacteria resistant to the antibiotics I added to the culture medium, so that only those bacteria containing the hybrid plasmids could survive. When I grew the bacteria on a growth plate containing antibiotics, if the experiment was successful, bacterial colonies would appear. Each colony was from a single bacterium, each carrying a specific copy of the mummy DNA. To check my experiment, I set up a control group, which is necessary in any experiment. I also repeated two identical experiments at the same time, except that one group did not add mummy DNA to the plasmids, and the other group added modern human DNA. After adding the corresponding DNA to the bacteria, I spread them on agar plates containing antibiotics and placed them in an incubator at 37°C overnight. As expected, the next morning, when I opened the incubator, I was greeted by a humid, culture-smelling air. The plates with modern human DNA were covered in thousands of colonies. This showed that my plasmid had worked: the bacteria survived because they carried the plasmid. In the experiments without foreign DNA added to the plasmid, almost no colonies grew, indicating that there was no DNA from unknown sources in my experiments. The group of experiments with DNA from the East Berlin mummy grew hundreds of colonies. I was ecstatic. Clearly I had copied 2,400-year-old DNA! But could it have come from bacteria living in the child's body, rather than her own DNA? How could I prove that at least some of the DNA I cloned in the bacteria came from humans?

I needed to identify some DNA sequence that would show it was human DNA, not bacterial DNA. But if I just randomly sequenced clones, some of them might come from the human genome (in 1984, the entire human genome had not yet been decoded, and scientists at the time had spent a lot of effort to sequence sporadic sequences), and some might come from some microorganisms whose DNA sequences were almost unknown. So I had to pick out some important clones to sequence, rather than just randomly choosing. What helped me solve this problem was a technique that could identify which clones contained DNA similar to the sequence I was looking for. The technique involved transferring some bacteria from hundreds of colonies onto cellulose filter paper, where the bacteria broke apart and their DNA adhered to the paper. Then I labeled the DNA fragment with a radioactive substance, making a single-stranded "probe", and then hybridized with the complementary sequence of the single-stranded DNA on the filter paper. The DNA fragment I chose contained a repetitive DNA element (the Alu element) and was about 300 nucleotides long. There are about 1 million copies of Alu elements in the human genome, but none in apes, monkeys, and other creatures. In fact, there are so many of these Alu elements that they make up more than 10% of the human genome. If I could find Alu elements in the clones, that would indicate that at least some of the DNA I had extracted from the mummy was of human origin.

One of the genes I had been studying in my lab contained an Alu element. I combined it with radioactive material and mixed it with filter paper. As expected, the clones contained radioactive material if they contained human DNA. I picked the most radioactive hybridizing clone, which contained a DNA fragment of about 3,400 nucleotides. With the help of Dan Larhammar, a DNA sequencing expert in my group, I sequenced a portion of the clone and found that it did contain the Alu element. I was delighted. My clones had human DNA, and they could replicate in bacteria.

In November 1984, while I was still struggling with sequencing gels, a paper that meant a lot to me was published in Nature. Russell Higuchi, who was working with Alan Wilson (the main architect of the "Out of Africa" ​​theory of the origin of modern humans and one of the most famous biological evolutionists at the time) at the University of California, Berkeley, successfully extracted and cloned DNA from the skin of a 100-year-old quagga (an extinct subspecies of zebra that still existed in southern Africa more than 100 years ago). Russell Higuchi obtained two fragments of mitochondrial DNA. He pointed out that, as expected, the quagga was more closely related to the zebra and more distantly related to the horse. This work greatly inspired me. If Alan Wilson also studies ancient DNA, and if Nature thinks that a paper studying DNA 120 years ago is interesting enough and worth publishing, then what I do is neither crazy nor boring.

This was the first time I sat down to write a paper about this research, which I was sure would be of interest to many people around the world. Inspired by Alan Wilson's example, I submitted it to Nature. I described the experiments I had carried out on the East Berlin mummies and listed my paper in the GDR magazine at the beginning of the references. However, before I sent the paper to Nature's London office, I needed to do something. I needed to talk to my thesis advisor, Per Patterson, and show him the paper that I had written and was ready to submit. With some trepidation, I walked into his office and told him what I had done. I asked him if he would be willing to be a co-author on the paper with me as his advisor. Obviously, I was overthinking it. Instead of blaming me for misusing research funds and wasting precious time, he seemed happy. He agreed to read the paper but refused to be named as a co-author, for the obvious reason that he had not been aware of the research before.

A few weeks later, I received a reply from Nature, saying that if I could respond to the reviewers' minor comments, they could publish my paper later. Not long after, the proofs arrived. At that time, I was thinking about how to approach Alan Wilson (who seemed like a god to me) and ask him if I could work with him in Berkeley after my doctoral defense. I didn't know how to start, so I sent him a copy of the proofs without any instructions. I thought he would be happy to see the unpublished paper in advance. I thought I would write to him later to ask if I could work in his lab. Nature moved quickly and even designed a cover illustration with a DNA sequence cleverly wrapped around a mummy. Even faster, I received a reply from Alan Wilson. He called me "Professor Paabo" - there was no Internet or Google at that time, so he had no way of knowing who I was. The rest of the reply surprised me even more. He asked me if I could visit "my" lab during the upcoming sabbatical year! It was a beautiful misunderstanding, all because I didn't include any introduction. I joked with my friends that Alan Wilson, the most famous molecular evolutionist, might wash my gel plates for a year. Then I calmed down and wrote him back, explaining that I was not a professor, not even a PhD, and did not have a lab for him to visit on sabbatical. Instead, I wanted to know if I had the opportunity to do a postdoc in his lab at Berkeley.

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