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Last autumn he was honoured with the Nobel Prize in Chemistry. But the next big discoveries risk being smothered under a layer of research funding red tape, according to Morten Meldal.
Morten Meldal rehearses with his band every Monday. Or: Morten Meldal used to rehearse with his band every Monday. The band is called Carlsband because it consists of people that Morten Meldal worked with at the Carlsberg Laboratory in the Copenhagen district of Valby, where he held a series of positions over four decades from 1988 until 2011.
On one wall in his office at the H.C. Ørsted Institute — the 1962 building that is home to the Department of Chemistry at the University of Copenhagen — is a home-made bass guitar and a regular guitar. It is the guitar that is his preferred instrument, but in Carlsband Morten Meldal has to make do with a role as rhythm guitarist.
»We have a great lead guitarist,« says Morten Meldal enthusiastically. »He can just do all the cool riffs!«
The professor sits in a sweatshirt from the University of Copenhagen, which is pulled over a shirt. And judging from all the photos taken of him in recent months (probably more than in all of his previous 69 years), the head of the Centre of Evolutionary Chemical Biology is a real company man: He always flashes the university logo.
When the Carlsberg band practices, each band member selects a handful of songs to play. A process where Morten Meldal is not always the object of undivided enthusiasm among his fellow players. He simply loves reggae, and the others don’t. But it has been a long time since they have had to choose songs. So long that the others might even have started to miss a round of reggae. They have, to be exact, not played even once since that day in October, when Morten Meldal was sat in front of one of his four computers in his office to prepare some teaching. (He owns about 30 of them in total, and, yes, he also builds them himself.)
It was like ‘Alice in Wonderland ‘ and ‘The Wizard of Oz’ at the same time.
Morten Meldal on the Nobel Prize ceremony in Stockholm
It was 5 October, a Wednesday, and outside it was a balmy 14 degrees, a bit damp, the sun was out every now and then, and his phone rang. It was a Swedish number. Two years earlier, at the same time of the year, a couple of his students who were preparing a revue played a nasty prank on him. They had called, and with a broken Swedish accent, informed him that he was the lucky winner of the Nobel Prize in Chemistry. So when the phone rang again during Nobel prize season, his first thought was that it was those god-awful students again. This time they had got themselves a Swedish number. But quickly – right away – it seeped in that this was, actually, it. And then a new thought struck him: The balance and the rhythm that he had painstakingly succeeded in establishing in his life after many years of difficulty: This would suddenly no longer be there. Until a new thought, or perhaps a feeling, washed over him:
»Then I thought: Damn, this is a real honour!«
One hour later – at exactly 12 noon – the news of the Nobel Prize was released to the rest of the world. And Morten Meldal could, in the entrance to his office where the tall man can barely stand upright, receive the applause of his colleagues and students. He still looked like someone who could not really believe it.
»A Dane doesn’t get the Nobel Prize every day, so it’s a big thing,« he said to the people there from the press. You can say that again. Over the last 122 years, only 15 Danes have been honoured with the prestigious award which, apart from the Peace Prize, is awarded in Chemistry, Physics, Physiology or Medicine, Literature and the Economic Sciences.
According to the Nobel Prize Committee’s announcement, Morten Meldal and the two American researchers with whom he shared the award, Barry Sharpless (Scripps Research) and Carolyn Bertozzi (Stanford University), received the award for the development of click chemistry and bioorthogonal chemistry. But what is this exactly?
It started back in 1999 when Morten Meldal was head of synthetic chemistry at the Carlsberg Laboratory’s chemical department. Under him, he had 20 different projects, all of which were based on a large centre grant from the Danish National Research Foundation, which Morten Meldal had won two years beforehand.
The grant included a 30 per cent new research a year requirement. As far as the 20 projects were concerned, Morten Meldal had not laid out a specifically defined direction, so long as it was about quantitative chemical reactions that could be combined with peptide chemistry. A work process that, when he looks back, has been symptomatic of his entire career.
»I’ve always wanted everything. In fact, it may have been a bit of a problem in my career,« he says. »And the strength.«
The PhD student Christian Tornøe was in charge of one of the projects in the laboratory. The project did not go as Christian Tornøe wanted it to, however. Not at all. When he set up his experiment each day, the reaction was completely wrong, or at least not as he had hoped. Disillusioned by three weeks of errors in his experiments, Tornøe went down to his supervisor, Morten Meldal, and told him that he was quitting. The PhD was a fiasco.
»Calm down, take it easy,« the experienced Meldal said to the younger Tornøe. And they went up to look at the experiment and study the results closely. No. The experiment didn’t lead to the desired reaction. But … there was something else.
»I could see right away that a different and very pure reaction in the experiment had taken place that was worth investigating,« says Meldal.
Throughout the years, up until now, organic chemistry had experimented with binding molecules together. Together, the molecules could have some desirable properties – like, say, as part of a drug. Not all molecules, however, want to have anything to do with each other. So if you wanted to bind one molecule to another, it sometimes required some extremely intricate detours via a large number of intermediate molecules, which was both complicated and not viable when you wanted to achieve the desired property in a concentrated form.
I've always wanted everything. In fact, it may have been a bit of a problem in my career. And the strength.
Now, in the laboratory out in the Copenhagen district of Valby, something was revealed that might let you skip all the troublesome intermediaries. An azide had unexpectedly reacted with an alkyne and thereby created a triazole, a stable and functional chemical structure that can glue together other types of chemical functionality. The explanation for the unexpected reaction was, Morten Meldal and Christian Tornøe found, that they had used copper as a catalyst.
»We could see that this was something extraordinary,« Meldal explains. He describes these years at the Carlsberg laboratory as the busiest in his working life. When I ask him whether the extra long days were linked to the fact that he had the feeling that they were on the trail of something groundbreaking, he responded:
»Ambition is not a driving force in research. It’s an interest in what you are doing that motivates you. And if this is not the case, you might as well go home.«
Six months later, Christian Tornøe was able to travel to the US and present the results. What they had created was the so-called copper-catalysed Azide-Alkyne cycloaddition reaction. Or as the American Barry Sharpless, who independently of Morten Meldal and Christian Tornøe was on his way down the same path over in the US, called it: Click chemistry. Now you could click molecules together or design multi-functionality, if you wanted to.
It was on the back of this invention that the third researcher Carolyn Bertozzi a couple of years later carved her name into the annals of history. She made the method bioorthogonal – human-friendly in other words. Copper is not suitable for living cells at all. But Bertozzi found out that if the alkyne is brought into a larger ring-shaped structure, the same reaction between the alkyne and azide (and thereby the production of the Triazole) can be obtained without the copper.
It is for these achievements – and their use in, say, the development of drugs and in diagnosing and treating cancer patients – that Morten Meldal, Carolyn Bertozzi and Barry Sharpless (for the second time), at a glamorous set up in Stockholm were honoured with the finest prize of chemistry: The Nobel.
»It was ‘ Alice in Wonderland’ and ‘The Wizard of Oz’ at the same time,« Morten Meldal recalls as he thinks back to his experience in the Swedish capital.
He stands up and picks up a stash of papers that have been clipped together in one corner.
»Take a look at this,« he says and slams the wad of papers on the table. It is the programme for the Nobel Prize ceremony from 5 to 12 December.
When Morten Meldal arrived at Stockholm Airport with his wife, Phaedria Marie St. Hilaire who works as a chemist at Novo Nordisk, they were picked up from the actual aircraft in a Volvo with ‘Nobel Prize’ inscribed on it and escorted to the Grand Hôtel in the central part of the city. (They had their two children with them also. Even though the Nobel Foundation – as per tradition – had arranged for rooms for them also, they had to make do with ordinary transport.) Here, the couple checked into a »huge suite,« as Meldal describes it, with a view over the Strömmen waterway and the royal palace.
Ever since the Nobel Prize was founded in 1901, the Grand Hôtel, which was opened in 1874 by the French chef Régis Cadier, has had a central place in the festivities: This is where the winners and their families stay every year. And it was here in the hotel’s hall of mirrors that the huge gala dinner used to take place, That is, until the event had taken on such proportions that in 1930 it had to be moved to the city hall where it has taken place ever since.
»It was all so new and exciting. It was exciting to deliver the speech. It was exciting to receive the award. And it was really exciting to meet the Swedish royal family,« says Morten Meldal. »They are really down-to-earth.«
What do you think you will remember the most when you, 20 years from now, think back on this week in Stockholm?
»The week will be like a dream where I can remember all of the different elements within it.«
As a boy, Morten Meldal was not a whiz-kid at school. For several reasons. If the teaching got too dull and repetitive, his thoughts wandered. And in his spare time he was far too busy with all sorts of other things to focus wholeheartedly on homework and this kind of stuff. Morten Meldal played music and listened to jazz fusion, and he painted and built stuff.
At the age of 12, when he was with his family at a summer cottage in Sweden, he got a hammer, a box of nails and some wood, and was told to build an outhouse. So he did. And on the island of Bornholm, where his grandparents owned a farm until it was expropriated by the military, he got dirt under his nails, and knees stained with green. The farm was also the home of a cowman, and together with his two eldest boys, Morten Meldal dug underground tunnels under the military site next door.
»We did a bit of spying,« he says with an impish look about him that is magnified behind a pair of glasses.
They were a couple of naughty boys, the sons of the cowman, so Morten Meldal was tricked into doing all kinds of stuff. Like when they jumped on to the back of the pigs and raced through the pigsty while they hung on to their ears. This was probably animal cruelty, he reckons now, since bacon pigs can’t stand being ridden on. And then there was the time when one of the two boys stole his granddad’s combine harvester and plowed through a stable wall.
On Bornholm, Morten Meldal was outside from dawn till dusk, and there were meadows, and woodlands, and a beach to explore, and he fell in love with nature.
»I can remember quite clearly when I was out there lying in a field of barley, messing around,« he says. »I was on the edge of the field, and there were a bunch of poppies and all sorts of weeds. And then there were these big green grasshoppers. And other insects, too. And I remember thinking: ‘How did they get to be like that? Why is it like this?’ Look at that: ‘Why is it like that?’ It has been in me since I was very young.«
A few years later, at home in his parents’ basement in Rungsted, he also built his own rockets. They were »the best ever,« and they »flew 300 metres up in the air and out into the Øresund with a white light on it.«
»In those days you could go down and buy a whole box full of explosives. This is not possible today,« he says, deadpan.
In this way, Morten Meldal took two interests with him from his young years, which he eventually would unfold and unite: A fundamental curiosity into how the world is put together, and a fundamental wish to build things. This goes for the engineering degree programme at the Technical University of Denmark (DTU), and when he moved into chemistry and learned that he belonged in the laboratory .
»It suddenly became very exciting,« he says.
If you ask Morten Meldal what chemistry is, he will answer: Everything.
»When I look around,« he says and gesticulates out into space, »there is nothing out there that for me is not chemistry.«
This morning, when he woke up early at approximately 04:30, he was dreaming of chemistry. Sometimes he solves a problem or a challenge in this way. But he does not have a block of paper on his bedside table to take notes of a solution. If he has first solved a ‘gap in his understanding’ in his head, he will not forget it again.
What do you think of, when you think of chemistry?
»I have a whole world in my head. And it’s a world that’s been built up over many years. It is three-dimensional, and the molecules float around in there.«
Is it beautiful?
»Yes it is, really beautiful. And the molecules are coloured in accordance with their properties.«
For Morten Meldal, chemistry is not just the key to understanding our world – and thereby also the key to solving many of the ongoing crises we face globally – it is also quite fundamentally fun, beautiful, and literally alive.
So Morten Meldal has little understanding for how we approach chemistry as a society. We learn it far too late as children — if it was up to him, kids should start it in the 1st grade. And when we finally get to physics and chemistry in the 7th grade, it is typically very »formula-oriented, very, very boring and a lot about rote learning.«
»It simply has to be made more attractive.«
How do you do that?
»I think — and I have not been given the green light for this yet — if we can get funding for a Danish Institute for Animation and Teaching, so that we get animations done about the world of chemicals, and whatever else you can otherwise imagine that is appealing to young people, it would make teaching it more enjoyable,« says Morten Meldal.
»We can’t see the chemistry, we can only see the results of it. The macroscopic results like us, these computers, the materials and so on. We can’t see what goes on at the nanoscopic level, but we can easily visualise it. And I think that you, for example, can personify hydrogen and oxygen as different personality types. With different qualities. One of them is a bit aggressive … the other smiles and is happy.«
Is this also how you see them yourself?
»Yes, it sure is.«
At university level, Morten Meldal has also learned that the general understanding of chemistry leaves much to be desired. In 2011, when he took up his position as professor at the University of Copenhagen, he found that the students – after three years on the chemistry programme – »knew nothing.« He restored a structure that really focussed on the chemists, »really teaching them things.« And the mission succeeded, he says.
When I ask Morten Meldal about his hopes and aspirations, he responds:
»I don’t really dream of achieving something specific. My dream is more about setting up a good environment here. And to help ensure that more people get a realistic appraisal of what chemistry is.«
This is one of Morten Meldal’s hobby horses: That chemistry should be more widely disseminated through a more enjoyable teaching.
The other hobby horse is the system that research is subject to. The way research funding applications happen. This needs to be redesigned, according to Morten Meldal.
Now he stands up in the middle of his office:
»We are completely wasting our time. And I am not lying when I say that I’ve written a pile of applications this high,« he says, and holds his right hand out from his hip (he is almost two metres tall). »Only three of them have been accepted.«
No: Less paperwork. More remuneration for good work. He outlines a system: Look at what a researcher has achieved with his latest research: If things have gone well, give them a stack of money to continue; if it has only gone so-so, give the researcher a smaller stack.
»In this way, you will get a self-regulating system that runs by itself. Without having to spend time on all this nonsense. And you will have a research environment that can react promptly to new discoveries. Because as it is today,« — now Meldal is really heating up – »you are planning for five years into the future. You just can’t do that.«
Morten Meldal is himself the living embodiment of his argument. His discovery of click chemistry was made on funds that specifically required new discoveries to take place. And that allowed for independent initiative and ingenuity. He talks about another time when he had got EU funding for a project. In order to ensure that everything took place as it was specified in the application, Morten Meldal had to have »some office clerk down in Brussels,« tagged on to him whose task was to tick off from a long list of sub-targets. And if the sub-targets were not achieved, the funding was cut.
»This stifles all initiative,« says Meldal. »It’s really harmful.«
I draw up an imaginary timeline on the table between us. I ask Morten Meldal if this means that if you make an interesting discovery with a greater potential than the original idea (like an azide that reacts with an alkyne and makes a triazole), then you cannot pursue that discovery?
»No you may not, no,« he says drily.
But that’s really stupid.
»You do it a bit anyway,« he says. »But this is not what is being encouraged. And it should be.«
He goes on:
»I can assure you that it is not always the best projects that are funded«
That’s sad. So all sorts of good discoveries and inventions are lost?
»That’s the way it is.«
Time is running out. And if there is one thing that Morten Meldal has not got more of since that phone call back in October, it’s time. He gets fan mail every day, and the pharmaceutical giant Novo Nordisk has suddenly dug up an application which Morten Meldal had sent them last year.
I ask him whether he looks forward to the time when all the hustle and bustle that has followed since the award is all over.
»No, there are a lot of things that I really look forward to. Lots of exciting travelling. First I have to go to Sweden and around their universities to do lectures. You need to do this. And I’ll be going to Vietnam. And then to Switzerland. And Bavaria. Then I’m going to Australia. And India. That’s exciting. But I just need to call the band.«
What is the number you are going to practice?
»I Shot the Sheriff.«