24 May 2016

Searching for the pill that will end snacking


Professor Birgitte Holst was already a dedicated researcher while still a student, and she was not even able to completely let go during her maternity leave.

By Mikkel Andreas Beck

Even when quite young, Birgitte Holst was fascinated by how the body functioned, and at the same time, she wished to help people who were ill. 

And so, studying medicine seemed an obvious choice for the now 44-year-old Professor of Neuroscience. She is, however, never actually face-to-face with her patients, instead she helps them long-distance, through her research. 

Today, she is group leader at Novo Nordisk Foundation Center for Basic Metabolic Research, where she conducts research on obesity and diabetes, or more specifically on the communication between brain and stomach. 

In 2003, she was part of the team that revealed what could be termed the uncontrollable snack-urge in the shape of the ghrelin-receptor, which is constantly trying to persuade the brain that there should be food on the table – even when the body does not really need it. By inhibiting the receptor with drugs, it may be possible to remove our inclination to overeat. 

Why did you become a researcher?

“I started researching while still a student, because I got a student job with Mette Rosenkilde, and it wasn’t long before I realised that it was really exciting. I spent practically all my free time there; it more or less became my hobby. It was the discovery of new aspects of bodily functions and especially how the various cells communicate that fascinated me. It still does.

“Before I completed my studies, I applied for PhD funding and immediately after that I was given a Postdoc, which meant spending a year and a half in the US. I’ve actually never completed my intern practice – it’s still out there, waiting for me,” says Birgitte Holst.

Why is your research important for society?

“There’s no doubt that obesity and diabetes are international and not merely Danish problems. It’s important to understand what regulates our appetite. What makes us eat the way we do, even when our body does not really need it. How do we put a stop to it – do we need drugs or do we need to change society?

“Everybody wants a pill that stops them eating too much or too much of the wrong stuff. The fact that we’re trying to understand what regulates our appetite allows us to intervene in different ways and generate an understanding of it not only being weak or stupid people who become obese. Humans are designed to eat more than we need. 

“The knowledge we can contribute may help ensure that people eat healthily and maintain a good level of physical activity from as early on as kinder garden.

“We’re also trying to find out what happens when we lose weight, as losing weight is not only healthy, especially not if you do it continuously. 

“Overeating is pleasurable and it makes us happy. The ghrelin receptor tells the brain to ‘eat some more’ after which you are rewarded with dopamine, which makes you want to do it again. We’re searching for the pill that will stop this desire for snacking without taking the pleasure out of eating,” Birgitte Holst explains.

Talk about a career high

“That would be when I was part of the group who discovered the hormone-independent signalling of the ghrelin receptor – it was most certainly a turning point. In short, it’s a receptor that continuously tells the brain that it’s hungry. It’s possibly the only known receptor that does not need a hormone to activate it, i.e. it generates unnecessary appetite.

“We were trying to determine which receptors where eligible for drug design. I was really supposed to have worked on a completely different receptor, but something went wrong. I had to work on the ghrelin receptor instead. I did a test and it revealed numbers that were nothing like what I expected. I remember thinking that someone must have turned something upside-down. The receptor shouldn’t have been as active without the presence of a hormone. But it was.

“That was how I ended up researching obesity, and it was really exciting. It was practically simultaneously with my first maternity leave, but I just had to be there when they ran the test again. So I parked my pram complete with sleeping baby in the secretary’s office, which allowed me to rush in and be a part of it.  

“Our discovery showed that humans have an inherent desire to eat even when we don’t need to. In terms of evolution, it’s quite clever that we’re programmed to store food – you see nice berries and you want to eat them. It’s just not quite as desirable when there’s enough food,” says Birgitte Holst.

What is the best thing about your job?

“It’s the continuous challenges. There’s no one straight path; you have to adhere to the data you receive along the way. I present a hypothesis, but the result turns out to be very different from what I expected, and then I have to venture down a new path. There’s an unpredictability, which makes it both challenging and exciting. 

“Furthermore, getting to make your own decisions, deciding on what you want to do, is also fantastic. You have to work a lot – I know no researchers who work less than 37 hours, but I decide the way forward, and that’s great.

“Oh, yes, and it’s actually really wonderful to get paid for working on your hobby,” Birgitte Holst adds while laughing. 

What do you do when you are not researching?

“I have three children, so I spent much time with my family and friends. I also spend a lot of time being involved in my children’s sports activities. I used to be an elite gymnast, so I know how much it means to them. I have a son who’s very keen on athletics and a daughter who’s a keen swimmer. So, I also run and swim a lot.”