Norway's Nobel neuroscientists continue to explore the secrets of the brain

It could have been any Friday at any workplace. Everything seems so ordinary. A non-descript building, just past a roundabout. In the kitchen, someone has spilled a little coffee. At the same time, it is anything but ordinary.  

In the same building where two Nobel Prize laureates work, rats are regarded as highly valued team members. The building also houses Norway’s only virus factory, where custom-made viruses are produced for use in neuroscience research.  

The Nobel Prize ceremony ten years ago is now a part of history. May-Britt Moser's stunning blue dress decorated with bejewelled neurons is frozen in time, displayed behind glass that the cleaning staff regularly dusts off. The Nobel Prize was never the goal, just a very inspiring stop along the way. It may have been a massive door opener, but it didn’t make the door any bigger; neuroscientists May-Britt and Edvard Moser still have to apply for funding, just like other researchers. Time and time again, they have to explain what they are researching and why. Application after application.  

“Discovering the sense of place was a monumental paradigm shift, but we couldn’t rest on our laurels,” says May-Britt Moser, a professor at the Norwegian University of Science and Technology (NTNU). Despite both being elite international researchers, they are also very much part of the public consciousness, and it feels natural to simply call them Edvard and May-Britt.  

The same offices 

She is sitting in exactly the same office as she did 10 years ago: a tiny one some way down a corridor. The most eye-catching thing is not all the books, but the walls themselves that are covered with photographs of smiling people with their arms around each other. The joy of being reunited. Job satisfaction. Some of the photos are taken in the United States, others in Asia or Trondheim. It is difficult to put a number on how many PhD candidates have passed through this office, but it is definitely in the hundreds. It is something of an international elite school for aspiring neuroscientists.  

He is in the same office he was in ten years ago. A bit bigger than hers, but down the same corridor. It is packed with books, but also lots of computer screens of various sizes. A bit like an air traffic controller for researchers. As Nobel Prize laureates, they travel quite a lot, but this is where they can be found most of the time: in the office in Trondheim, discussing things with their fellow researchers, writing research articles, and looking for answers to questions that no one has asked before. Step by step.  

Over 100 employees 

When they first started, they were the only employees. Today, however, there are over 100 people employed at the department.  

“We have several mottos that we try to live by. We shall conduct excellent research. Our co-workers shall be happy. Our animals shall be happy. We shall also have a diverse group of co-workers. You can’t make progress if you clone yourself. We have made progress because we have dared to bring in brilliant people who specialise in completely different things than we do,” explains May-Britt. 

Once upon a time, they were husband and wife. Now they are proud grandparents and good colleagues. When he is stuck trying to answer a difficult question, it is May-Britt he calls. When she is stuck trying to answer a difficult question, it is Edward she calls. No rings on their fingers, each living at their own address, but still life partners in science. The day begins with a telephone conversation. During the day, there is often a meeting where both attend. After work, they talk on the phone again. Sometimes they meet for a meal together.  

A lifestyle 

“It is a pleasure to work with Edvard. We have gambled all the way, and many times it has been a bit scary. We have wondered if we would be able to raise our children, get a house, and how we would manage to earn a living. The only certain thing we have done is to educate ourselves as clinical psychologists. Everything else has been high-risk. But we have been greatly rewarded by being able to spend our lives on what matters most,” says May-Britt.  

“Working the way we do is a lifestyle, but there are many professions that are more of a lifestyle than a job. In my 20s, when I was just starting out, my only dream was to get a permanent position as a researcher. I am privileged to be able to work with what I am passionate about,” says Edvard.  

A tiny microscope 

They have dedicated their lives to what could be regarded as a gigantic jigsaw puzzle. No one knows how big it is, how many pieces there are or how many are missing. There is no picture on the front of a box showing how to put the pieces together. The only certainty is that the entire puzzle must be completed. Piece by piece.  

This is how all basic research takes place. Each discovery is a piece whose exact place in the puzzle is not known when it is found. In brain research, there were very few pieces in place when May-Britt and Edvard started in the 1990s. And that was part of the allure. May-Britt and Edvard have now managed to put many pieces of the puzzle together, but many are still missing.  

“We are trying to answer the big questions about how brain cells communicate. It is a great responsibility that weighs heavily on our shoulders with all the money, the people, and the research we are involved in. Sometimes I wake up at night wondering if we have stayed true to our vision, but the new discoveries we make are really exciting,” says May-Britt.  

Both of them believe that the discovery of grid cells is one of the most important pieces of the puzzle. It was this discovery that earned them the Nobel Prize, but there have been several other important milestones along the way. The discovery of grid cells must share first place with the discovery of how large groups of cells communicate with each other, enabling us to navigate within a house, for example. To achieve this, they have developed a tiny microscope. The entire microscope is so small that it weighs the same as just half a teaspoon of flour.  

The development of the microscope happened long after King Carl Gustav of Sweden awarded them Nobel gold with great pomp and ceremony in 2014.  

A window into the brain 

To explain, we need to go back in time with Edvard and take a taxi ride. After attending an international conference, he was invited to a laboratory in China. The head of the laboratory sent their best student to get Edvard. Any recruiter would have loved to have overheard the conversation in the backseat of the taxi, because the outcome was that Weijian Zong, who is both a brain researcher and an engineer, packed up his entire life and moved to the capital of Trøndelag.  

“We look for creativity. And of course, you must have a passion for the job,” says Edvard.  

Before Zong arrived in Trondheim, the laboratory rats had to be studied under a microscope that was as big as an MRI scanner; the type you have to lie inside if you are having a knee or hip examined at the hospital. The rats now have the microscope placed directly on their heads, like a window through which we can see directly into their brains.  

With the old technologies used until just a few years ago, you could only study one cell at a time. It was like picking one flower after another when you are out in a meadow. The new instruments attached to the rats’ heads enable the researchers to film their brains directly, capturing thousands of cells at a time. The researchers are able to harvest the entire meadow in one go.  

A cure for Alzheimer’s? 

Of course, this means they now have a huge bouquet to keep track of. The only solution is to embrace artificial intelligence and powerful computers that can process and interpret the swathes of data being harvested. But these don’t exist yet. So someone has to make them. And that is what they are doing: checking every possible combination, piece by piece. 

No one knows when the puzzle will be complete or what might happen then, but somewhere along the way, the challenges of Alzheimer’s and a number of other brain diseases will be addressed and resolved. At some point in the future, people will no longer lose themselves in the fog of dementia. Once and for all. However, the hope of there being a cure at some point in the future doesn’t help desperate relatives here and now. Moser and Moser regularly receive handwritten letters expressing a cry for help. May-Britt even had to switch to a secret phone number.  

Alzheimer’s – one of the goals 

“We just have to keep working towards our long-term goals. The fruits of what we are working on will come much further down the road. We are not doctors and don’t have much advice to give right now,” says Edvard.  

“Fortunately, people understand that in order to find solutions, we must first understand how the brain works. You can kind of compare it to a broken washing machine. In order to be able to repair it, you first need to understand how it works. People are so friendly. When I’m out shopping, people often come up to me, pat me on the shoulder and show genuine interest in what we are working on,” says May-Britt.  

But just as the Nobel Prize wasn’t the goal, solving Alzheimer’s disease isn’t the ultimate goal either. It is much bigger than that. What May-Britt and Edvard are trying to figure out is how communication between nerve cells in the brain enables us to remember things like a childhood friend’s birthday. Or why the smell of gingerbread evokes very specific memories of Christmas.  

“Ever since I was a child, I have wondered why animals and humans do what they do. We want to understand this by discovering how many thousands of brain cells work together,” says May-Britt.  

“What we call thinking, memory, planning, and decision-making are quite advanced functions that we sometimes refer to as intelligence. We want to find out what brain cells do to achieve these functions. That research will explain to us what happens in a normal brain, but also what happens in a not-so-normal brain,” says Edvard.  

Custom-made viruses 

In addition to the new instruments, viruses play a key role in the quest to understand how brain cells communicate.  A few floors above the offices, we find Norway’s only virus factory. There, the brain researchers produce custom-made viruses that help in the quest to find out how brain cells talk to each other. With the COVID-19 pandemic still fresh in our minds, it sounds almost too outlandish to be true, but before May-Britt and Edvard created their own virus factory, the viruses they use in their research were imported from the United States. These viruses cannot infect or replicate, but instead act as tiny delivery trucks that transport a gene into the brain cells.  

The rabies virus, for example, is an expert at moving backwards and against the flow through the nerves, from cell to cell, and into the brain. Once the virus has transported the gene into the brain cells, the gene is incorporated into the cells and starts doing its job: turning genes on and off. This enables the researchers to study which cells do what inside the brain through the microscope. 

Another way of studying which cells do what is by filling the rats’ brain cells with a fluorescent protein. It basically makes the brain cells light up when they are active. Like a reflector in the dark.  

“This process doesn’t affect the animals in any way. Imagine looking down at the surface of a brain upon which there are several hundred cells. There may be many levels, and each cell is a dot that lights up when it is active, enabling us to observe which nerve cell does what,” explains Edvard.  

The lab and the dog 

Even Nobel Prize laureates who are passionate about solving the mysteries of the brain have a life outside the laboratory. That is just the way it is. They both live by the sea. They both love concerts and culture. They both unwind by enjoying the great outdoors. Edward is fascinated by volcanoes. He loves standing on the edge of an active volcano, gazing down at the red-hot, bubbling lava. 

“It is the thrill of active volcanoes that I enjoy. I have visited quite a few of the world’s active volcanoes,” says Edvard.  

Nine years ago, a new man entered May-Britt’s life. His name is Fado, and he is a lovely springer spaniel.  

“I wish there were more hours in the day. The balancing act of having a dog, living alone and having a busy job doesn’t always work out, but you just have to make a choice about what is most important. For me, it is the lab and the dog. Fado needs to go for a walk and the research has to be done. They are the most important things. Or maybe it’s the other way round: how would I survive without a dog?