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Milk is Great

Improved infant formula. A remedy against cavities in the teeth. Help with wound healing. Food for astronauts. The discovery of the OPN protein in milk turns out to have great potential and so far it has resulted in three patents for the University of Aarhus.

In this part of the world, we were all brought up believing that drinking milk is good for you. Even beyond the age when other creatures in the animal kingdom have been weaned.

Now senior researcher Esben Skipper Skørensen from the University of Aarhus has discovered that milk is even better than we thought. He has found a protein, osteopontin, in normal cow’s milk that has a number of extremely beneficial properties that can benefit us all in different and even surprising ways.

Esben Skipper Sørensen is a protein chemist and a project manager at the Laboratory for Protein Chemistry. Even since his students days, he has been interested in proteins and their structures. He says:

“First of all, it turns out that osteopontin called OPN, is also found in breast milk and in much higher quantities than in cows. A litre of cow’s milk contains 20 mg osteopontin whereas a litre of breast milk contains 138 mg. The content varies considerably from one woman to another and some women have up to 400 mg OPN per litre in their milk.”

The Aarhus researchers were the first in world to discover this: “It made us think that OPN, which plays a role in the immune system, could be one of the reasons why breast milk is so much better for infants than cow’s milk,” says Esben Skipper Sørensen, “but at that stage we didn’t consder what is could be used for – we just wanted to study it.”

It all began when he was about to write his thesis in 1991. When his supervisor handed him an article on milk proteins and asked him whether that would be of any interest, he jumped right in.

Refined technique

About that time, researchers at the Department of Molecular Biology launched a so-called plasmin project largely financed by MD Foods, now Arla Foods. Six months later, Esben Skipper Sørensen joined the project, and within two months he had isolated two new milk proteins.

“It was originally a blood laboratory, and we applied the same techniques to the milk as the ones used for the examination of blood. In the food laboratories, basically, they looked at the milk proteins, which they thought of as primarily a food source.  They had never previously looked at milk in the light of molecular biology, but our techniques for identifying a new protein were very, very refined,” says Esben Skipper Sørensen, whose specialty is the cleaning and characterisation of proteins.

Three patents

One of the two proteins that Esben Skipper Sørensen had found was osteopontin. That discovery alone has already resulted in three patents: the first concerning ways to derive OPN from cow’s milk; the second about how to use it in infant formulas, and the third relating to ways to use it to prevent holes in teeth.

Esben Skipper Sørensen and Arla jointly hold the rights to the cleaning of osteopontin. That was established before the year 2000 when researchers held all the rights. He has been bought out by Arla but may later be paid royalties.

Esben Skipper Sørensen explains that it is a huge operation to produce OPN and that is requires a company the size of Arla to do so. The reason is that it takes 50,000 litres of milk to produce just one kilo of OPN.

He continues: “You concentrate the whey, but the trick is to find a logical point in the process because how do you extract it without wasting a lot of milk? You have to use it all, so after extracting the osteopontin, you use the rest of the proteins as filing in processed foods, e.g. in liver paté. If the demand becomes very high, we won’t have enough cows’ milk in Denmark.”

However, OPN in breast milk was not the final option, and Esben Skipper Sørensen says that this exciting protein presents many more possibilities.

Can prevent caries

“It is true that OPN strengthens the breakdown process that takes place in the bones, but it can bond with minerals and calcium that make up bones. I therefore thought to myself: What about the teeth? Maybe it can prevent carries?” he says.

“I spoke to a couple of dentists and we discovered that osteopontin regulates the biofilm, i.e. the layer of bacteria that lives on the surface of the teeth, and helps maintain a natural balance in the mouth. OPN can control the composition of bacteria in the biofilm, impairing the growth conditions for harmful bacteria and making more room for good bacteria. It therefore creates a better balance, and our work hypothesis is that it will result in fewer cavities in the teeth.”

The Aarhus researchers and the Faculty of Odontology in Malmø are currently conducting a number of studies to find out if the theory holds water.

If so, the osteopontin needs to get in the mouth in order to work. Esben Skipper Sørensen has therefore also contacted manufacturers of chewing gum, and they have already discovered that the release is good, i.e. that the chewing gum releases the osteopontin.

Toothpaste is also an obvious possibility: “You get a dose in your mouth and there is sufficient time for the osteopontin to settle on the teeth,” he says.

Collaboration with Arla

Esben Skipper Sørensen and his researcher colleagues have been working with Arla all along, and the company has invested a considerable amount of money in this research.

“Contrary to what others do, we started with the industry. We went to Arla Foods and said: “We have something you might be able to use.” It is often the other way round with a company approaching the university, asking the researchers to solve a specific task.”

“I was introduced to people at Arla while I was still working on the completion of my thesis in the early 1990s. That is how it all came about. To get something like this up and running, you must have known each other for a while and trust each other,” he says.

As long as it works

“At one stage, the dairy companies said: “All of this research is fine, but now we want something tangible to come out of it”. For many years, I felt like I was whistling in the wind at Arla – that they didn’t believe in it, but of course, medical use it not their core area and it requires many resources. They say they don’t care, as long as it works.”

However, the results speak for themselves and Esben Skipper Sørensen is of the opinion that milk proteins have considerable potential:

“Arla has enormous development potential within bioactive milk proteins. In the past, they haven’t had a receptive system – they have been short of molecular biologists, for example. They have now started employing people from the university and therefore have a system that is more receptive to our ideas. And that is how it should be. We forward the knowledge we produce through research to the industrial sector so that they can develop the projects commercially. This only works because we have known each other for a very long time.”

A patent is not the aim

Esben Skipper Sørensen is not keen on research that is targeted or follows established guidelines. “You cannot agree today that that you want to work on a specific project for the next four years and specify milestones – I don’t believe in that. It is the long haul that matters. All the project managers who are employed are forever making phone calls, talking and organising – it is a mentality that stems from business college, but it can kill a project because the project managers lack understanding of the actual research process. It also kills all related ideas that are generated along the way and which might actually be better,” he says.

“A patent should not be the aim of research,” says Esben Skipper Sørensen: “You ought to say: my job is to carry out research and get good ideas – others, in this case Arla, will have to look after the patents.”

These patents have also benefited the University of Aarhus, as Arla has entered into a royalty agreement with the university.

Space food for astronauts

One of the possibilities of osteopontin is that it can potentially be used for treating wounds, both because the protein has an effect on the immune system and because it helps control the so-called collagen fibrils when they create new skin. A PhD student is currently working on that project.

In a truly spectacular trial, the Department of Molecular Biology and Arla are collaborating with the European Space Agency, ESA, in order to determine whether osteopontin can help maintain astronauts’ physiology during space travel. The problem is that when astronauts are weightless, they lose bone and muscle mass and their immune system deteriorates. They therefore need food that can counteract this.

In addition, osteopontin can potentially be used in connection with bone implants.

Esben Skipper Sørensen says that the possibilities in connection with osteopontin research are far from exhausted. However, if you ask him whether he has always wanted to be a researcher, he says: “I have always known that I wanted to be a biologist, but a researcher – not really…”

While writing his thesis, he was nevertheless one of the first students to be admitted to the newly created “4 plus 4” PhD scheme, which is aimed at researchers at the University of Aarhus. In that scheme, students begin studying for their PhD before completing their Master’s degree.

And what was the subject of his PhD? Proteins, of course. Esben Skipper Sørensen is used to juggling many things at a time, and when he is not working – which is a lot of the time – he is a ‘very committed’ soccer coach for 24 boys aged 10 to 11 years. One of the boys is his own son.

This story appeared in ”From Idea to Reality – 12 researcher stories” by Birgit Brunsted and Gert Balling (ed.) Copyright Birgit Brundsted and The National Network for Technology Transfer and Forlaget Hovedland 2008. Reprinted with permission. Photo by Henrik Petit. Find out more about the book ”From Idea to Reality – 12 researcher stories” at www.techtrans.dk.

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Revideret 02.12.2015