Aarhus University Seal

JUST AS WELL I DIDN’T GET THE NOBEL PRIZE AT 40

Aarhus University’s only Nobel Prize winner, Jens Christian Skou, recently turned 90. He is slightly hard of hearing, but apart from that, most people find it hard to keep up with Skou both physically and intellectually. The Nobel Prize in Chemistry in 1997 was the pinnacle and the culmination of a research career that was never planned. CAMPUS talked to Skou about his childhood in Lemvig, his young days in Copenhagen and Hjørring, and of course the ground-breaking research at Aarhus University.


By Hans H. Plauborg
hhp@adm.au.dk

A small grey VW Lupo is parked outside Jens Christian Skou’s home in Rislundvej, Risskov. This is the reliable economy car par excellence, which is so fuel-efficient that it can get more than 30 kilometres per litre. It is the natural choice of car for the now 90-year-old professor emeritus from Aarhus University, who was awarded the Nobel Prize in Chemistry in 1997 for his description of the sodium–potassium pump. The scientist and the car simply go together. Throughout his life and his career, Skou has also been exceedingly reliable, and has utilised his fuel exceptionally well. Never a matter of long, fatiguing working days at the university, filled with coffee breaks and discussions with colleagues in the laboratory until long into the evening. On the contrary, more a case of getting up early, seven to eight hours of efficient and disciplined work, and home to tea with the family at four in the afternoon. And never a question of putting a strain on the family in body and mind by working at weekends. More a matter of topping up his energy levels by means of tennis, badminton, sailing and many other sporting activities.
“The freedom to choose my own work assignments and plan my life has without a doubt been the most important factor in my life as a researcher. I’ve also always had a great need to indulge in exercise and leisure activities, which meant it was good having a job at the university,” laughs Skou, who celebrated his 90th birthday in October. And if it wasn’t for the fact that it says 1918 in his birth certificate, nobody would believe that the man who so youthfully runs up and down the steep stairs in his home, looks after his sizeable garden and – helped by his 83-year-old wife Ellen Margrethe – tends a couple of acres at their holiday home in Mols, actually saw the light of day even before the last shell had been fired on the Western Front during WWI. Skou’s physique is quite simply in a class of its own, something achieved by a combination of good genes, a large amount of luck and applying discipline and moderation throughout his life. But why was the Lupo allowed to replace the black bicycle that was always his faithful means of transport? Surely he hasn’t grown too old for that?
“No, but I nevertheless decided to put it aside a few years ago, after I’d been rammed by a motorist making a right-hand turn on the ring road. It gave me quite a fright, so I bought the Lupo. My wife doesn’t like it, so she’s got another one,” says Skou, as we sit in his little study on the first floor of their home in Risskov. Only his hearing is not what it used to be, but we have to continue the interview without technical devices because the power supply has run out for the microphone in his hearing aid. Meeting with Maunsbach Lying on the table are Skou’s recollections – in manuscript form. There is no doubt whatsoever that an important part of his recollections are about his long working life as a researcher, which – on 15 October 1997 – led to the greatest tribute any scientist from Aarhus has ever experienced: the Nobel Prize in Chemistry. That was the day the modest and unassuming son of a timber merchant in Lemvig received a phone call from his boss at the Faculty of Science, Dean Arvid B. Maunsbach, who wanted to see Skou in his office for a meeting at 14.00.
“I told him that I really couldn’t make it because I’d arranged with my wife to go for a walk in the fine autumn sunshine. I’d been retired for a long time, so I felt I was entitled to say no,” says Skou. However, Maunsbach insisted and Skou cycled somewhat reluctantly to the university. He presumed the meeting was about appointing an assessment committee for a new professorship in biophysics. In fact it was, but he was nevertheless prevented from leaving afterwards.
“I got a bit annoyed and said there was no more to talk about, and so I left. When I got to the car park, a car pulled up and a man got out asking for me. I identified myself, of course, and he handed me a huge bouquet of flowers. I’d celebrated my birthday on 8 October, so I thought it was a bit late to be giving me flowers. However, Maunsbach then came out and said, ‘Jens Christian, it’s the Nobel Prize. We have to go back to my office and wait for the phone call from Stockholm’.” And so they sat there and waited and waited. For a phone that was supposed to ring, but didn’t.
“I thought I’d end up just like Karen Blixen, when she sat listening to the radio because she thought she was going to get the Nobel Prize, but it went to someone else.” However, the phone finally rang after all.

Can you remember what your first reaction was?

“The first thing that raced through my head was whether is was actually warranted. It’s very uncomfortable getting something you don’t deserve. I think I said something like they could have given the prize to a younger man. But I quickly decided not to think about whether or not it was deserved,” says Skou, as we look at pictures from those hectic October days 11 years ago. One of them shows the 79-year-old Nobel Prize winner signing an autograph for a female fan.
“Having to sign autographs was really quite exciting. There was tremendous commotion about that prize, and it actually continued for two or three years afterwards,” says Skou.

The road to research

It is hardly written in the stars about anyone that they will one day stand with a Nobel Prize for science in their hands. In Skou’s case, there was not even the least bit about research. On the contrary, “timber merchant” was clearly written all over the starry sky.
“I was the eldest son in the family and was very interested in the timber merchant business run by my father and his brother. If my father hadn’t suddenly died of an infection when I was 12, I would almost certainly have been a timber merchant,” he says. Instead, the business was taken over by his uncle, who was succeeded by his sons. Skou himself had to find something else. One day, a new young man turned up on the tennis court in Lemvig, with the fine title of “medical student”.
“He keenly told me what it was like to study medicine in Copenhagen. That’s what I wanted to do, so I told my mother. She was immensely pleased to hear it because I suppose she was getting a bit anxious that I couldn’t decide what I wanted.” The years as a medical student in Copenhagen were a great experience for the lad from West Jutland, who had matured after three years at boarding school on the island of Zealand from 1934 to 1937.
“I really enjoyed living and studying in Copenhagen. There were plenty of cultural temptations, and I went to lots of art exhibitions and performances at the Royal Danish Theatre. I’d heard that studying medicine was very hard, but I really enjoyed it. It was a matter of just sitting down and reading everything that had to be read.” However, the need to be close to the North Sea did not vanish during Skou’s period studying in the capital, so when he had to do his internship, he chose the hospital in Hjørring.

“Workwise, this was a fantastic period – possibly the best in my life. Being a doctor interested me greatly. I was especially fascinated by the craftsmanship involved in surgery. My boss at the hospital was in the resistance movement, so whenever he had to gather up the weapons dropped by the British, he would say, ‘You can finish off now, Skou,’ and I was allowed to do different operations.” His stay in Hjørring had given the young doctor ambitions. He wanted to be a surgeon and subsequently a consultant in this field. At that time, however, this required writing a dissertation, so he was encouraged to apply for a position at the Department of Physiology in Aarhus – and he got it. He had taken the first step into the world of research and education. However, being a lecturer and researcher was somewhat difficult, remembers Skou.
“You see I’d never done any teaching, and I quickly realised I wasn’t very good at it because the lecture theatre was empty by the time half a term had elapsed. This gave me something to think about. I could remember from my own studies in Copenhagen that I couldn’t be bothered going to lectures that I got nothing out of, so I started familiarising myself with educational theory, and how to go about planning good teaching. After a while, I actually got to be quite keen on teaching,” says Skou. And if it were not for his West Jutland modesty, he could have added that he did it well. After having him as a lecturer for several years, some of his students gave him a rocking chair in recognition of his good teaching.

The university in the 40s

It turned out that research did not come naturally to Skou either, even though he had conducted a little research in Hjørring into the treatment of headache following a spinal anaesthetic.
“My first attempts in the world of research didn’t turn out very well. But I’d become very interested in knowing more about anaesthetics. Back then in the 40s, there were no anaesthetists like there are today, so you used chloroform or ether as an anaesthetic, but it was an unpleasant experience for the patients. It was therefore better to give a spinal or local anaesthetic if you could get away with it. The question was just which mechanisms were behind the local anaesthetic. That’s what I wanted to find out.”

What was the Aarhus University environment like back then in the mid 40s?
“At the Department of Physiology, there were a professor, two research assistants and me. We didn’t have any mutual meetings, but just went our own ways messing around with things. The professor told me that if I had anything to ask about, I could just come to his office. Otherwise, I could do as I pleased. We had no shared activities, either social or academic. When he died and I had to write an article about him, I found out that he’d also been researching active transport between cells, just like me. I knew nothing about this and I doubt whether he had any idea about what I was doing. The university was a completely different world from the one I’d met at the hospital, and I had to grope my way forward.”

But you didn’t immediately apply to go back to the hospital world?
“No, no. I’m not like that. By that time, I’d got going and also had to write that dissertation.” The dissertation dealing with the correlation between local anaesthetic properties and their solubility in fats was submitted in 1951, which actually meant Skou was ready to go back to the hospital system. However, research had whet his appetite. His curiosity had been roused and he wanted to delve deeper into how anaesthetic agents actually work on nerve cell membranes.
“I’d applied for a position at Bispebjerg Hospital’s surgical department and got it. But I could very much sense that I’d come so far with this research that I couldn’t just give it up, so I asked my wife if it would be all right to do a bit of research in the evenings. Fortunately, she was more realistic than me and said that it probably wouldn’t be satisfying. So I called Bispebjerg and apologised for the inconvenience. It was basically pretty arrogant to do so because getting a job as a doctor was very difficult at that time. A researcher’s salary was also much lower than a doctor’s. In those days, a researcher’s salary was said to be the equivalent of an auxiliary postman’s. Luckily, I was able to supplement my pay by taking a few night shifts as an emergency services doctor in Aarhus. In the morning, I went straight to the department without getting any sleep,” says Skou, as if it were the most natural thing in the world.

Crabs and pumps

Ellen Margrethe has set the kitchen table with plunger coffee and bread, so we leave the study and go downstairs.
“I don’t really understand why you want to sit up there,” she says, while the photographer shifts things around in the kitchen.
“Do you really need more photos?” asks Skou, when the photographer starts snapping away again. However, he quickly forgets the camera when conversation once more focuses on his pioneer research, which picked up for real in the 1950s. Skou decided to conduct an experiment with a so-called monomolecular layer of nerve fats on a water surface, so as to test their ability to absorb local anaesthetic. He hoped to find out why the nerve impulse is blocked and the local anaesthetic sets in. It was already known that the nerve impulse is caused by an opening in the nerve cell’s membrane, through which sodium flows. It was also thought that sodium enters the cell via certain channels, but how does it take place? Following the experiment, Skou concluded that the sodium channels are a protein, but in order to study that protein in more detail, he had to get hold of an enzyme with a high level of activity. By coincidence, he read an article about ATPase in giant squid nerve membranes, during a period of study at the Marine Biological Laboratory in Woods Hole, USA, in 1953. ATP powers cells, acting like a fuel in which energy is released by splitting off a phosphate from ATP by means of an enzyme – a so-called ATPase. However, Skou wondered what role an energy-releasing enzyme could play in the nerve membrane. When he got back to Aarhus, he immediately began targeting suitable animals in his search for such an ATPase. Getting hold of giant squid was not an easy task, so he made an agreement instead with a local fisherman in Norsminde, who could supply crabs from the Bay of Aarhus.
“The biggest problem to start with was how to kill them. I tried using a hammer, but that meant there were crabs everywhere, and I need to use the nerves in their legs. I ended up by cutting off the legs and tossing them straight into boiling water so they died. The drawback was the smell of boiled crabs right through the department. My boss, Professor Ørskov, asked several times whether I could have found another test object, but by then it was a bit too late,” says Skou about his famous and infamous crab experiments. Unfortunately, Skou had difficulty reproducing his results.
“You see I was interested in the effect of local anaesthetic agents on the nerve impulse, and I felt it was obvious to investigate whether sodium and potassium had any effect on the enzyme activity. The problem was just that the results varied considerably every time I added sodium or potassium.” However, after a seven-week summer holiday in 1955, Skou came back with renewed energy. It struck him that he had concentrated on sodium and potassium individually, so he began conducting new experiments.
“I found out that sodium on its own slightly increased enzyme activity, and thus the rate of ATP splitting, and potassium had no effect at all, but a combination of sodium and potassium resulted in a considerable amount of enzyme activity.” Skou wondered whether the enzyme could have something to do with the interior of the membrane, which led to the nerve impulse, but soon realised that this could not be the case. On the contrary, the experiments implied that the enzyme could be involved in the transport of sodium out of the cell and potassium into the cell, a necessary process for maintaining a lower concentration within the cell than outside. In other words, his enzyme must be involved in the active transport of ions across the cell membrane and into the cell itself. The enzyme had to act as a kind of pump – hence the subsequent name “the sodium–potassium pump”.
“By this I meant that I’d discovered something new, and wrote about it in my article published in 1957. But nobody at all believed in it. They asked how on earth an enzyme could transport ions. An enzyme can act as a catalyst for a process, not as a transport system. I was all alone in my opinion,” remembers Skou.

Cheated by a colleague

His article with the impossible title The influence of some cations on an adenosine triphosphatase from peripheral nerves was not bedtime reading material for very many researchers. The theory about a pump function in the membrane of nerve cells had been promoted since 1941, but nobody had found any proof, so why should Skou from Denmark have done it?
“There’ll always be resistance to new viewpoints in the world of research. I can remember being both stubborn and somewhat frustrated back then. So it was good having some teaching to fall back on. When it went well, you could think it was OK, you were at least doing work that provided results.” The breakthrough for the idea about the pump came following a conference, when Skou was talking to an American researcher colleague he had met in Woods Hole in 1953. This colleague was convinced that Skou had demonstrated that the enzyme was the transport system, and he wrote an article in 1960 about his own experiments with active transport in red blood cells. He used Skou’s findings from the crab experiments, but “forgot” to quote that Skou had demonstrated in his 1957 article that the enzyme had something to do with active transport.
“I was pretty upset about that. I thought I’d been too naive and didn’t know how competitive research is,” says Skou. However, the story had a happy ending. At a joint gathering, the American colleague apologised for his “misdeed”, and the editors of the renowned scientific journal Physiology Review, who were presumably well aware that the American had not treated Skou very fairly, now asked Skou to write a front-page article about enzymes as transport systems. Following this, there was no longer any doubt. Danish Skou had discovered the pump that facilitates the transport of ions across the cell membrane, and is the cause of the tension difference required for nerve impulses and muscle contractions.

Pinnacle and culmination

The rest of Skou’s research career was spent understanding the implications of the mechanism he had discovered. In his typically modest fashion, he hastens to add that that he did not make any ground-breaking contribution to the continued work. And he possibly did not do so in terms of pure research. However, he got research into ion pumps to flourish at Aarhus University, and the university’s PUMPKIN basic research centre, under the direction of Professor Poul Nissen, is one of the absolute leaders in this research. In 2007, Skou’s heirs thus managed to clear the front page and most of the contents of an edition of the journal Nature with their proof of what ion pumps look like and how they act.

Skou himself first completely stopped carrying out research after he had turned 80. In the years following his retirement, he continued doing theoretical work. This included learning programming, so that he could go over different models himself.
“When I turned 85, my wife said that I now had to stop giving lectures, and I agreed with her. You shouldn’t wait until they’re sitting out there in the lecture theatre and saying to each other: ‘He shouldn’t have held that lecture’.”

What did the Nobel Prize come to mean?
“Well, it was both the pinnacle and the culmination of my work. During the subsequent two to three years, it meant that I couldn’t do any more than give lectures and all sorts of other things connected with the Nobel Prize. I was well on the way to calculating a whole lot of data, and I was happy with this, but the Nobel Prize severed the bond, so I was unable to return. In this way, it’s just as well I didn’t get the Nobel Prize at 40 or 50. That would have ruined my career.”

Would you have gone on with your research if you hadn’t got the Nobel Prize as a 79-year-old?
“Yes, definitely. In that case, I’d have continued for a few more years.”

Destructive research financing

During the last couple of years, Skou has been involved in a fierce debate about the financing of research. He believes it is destructive for research that researchers nowadays are forced to spend a considerable amount of time applying for external funds for their work. And on many occasions, he has said that if he – back then – had been subjected to the conditions applying today, he would never have received a Nobel Prize, simply because he would have left the university.
“With the current system, there’s a risk that the very research that could be interesting doesn’t even come about, but ends in the pile of projects not worth supporting. When I claimed that an enzyme can transport ions, people said I was talking nonsense. Under the current system, I’d never have got any money to study that. People forget that research is like drilling for oil – the platform that produces oil must have the necessary funds, of course, but everyone knows the well will dry up one day. You therefore have to keep drilling for new wells, running the risk that there’s nothing there. When the oil gushes out, it frequently makes up for the expenses involved in futile drillings,” says Skou, who has gradually stopped spending time trying to get politicians, in general, and Helge Sander, the Danish Minister for Science, Technology and Innovation, in particular, to understand what research is all about.

Instead, he has spent time writing his memoirs and looking after his garden – both the one in Risskov and the one at his holiday home in Mols.
“This summer, I also tried playing tennis again for the first time in a number of years. My daughter had started, so I just had to try and play against her. But it was simply a fiasco. I won’t be venturing onto the tennis court again,” laughs Skou.