Perspectives – growing our knowledge

Researcher profile: Jöns Hilborn

Jöns Hilborn works at the Ångström Laboratory – in close contact with engineers, chemists, materials scientists, biologists and physicists. PHOTO: MIKAEL WALLERSTEDT

Knowing how to combine life-determining molecules

Bone healing, cancer treatment... the list of Professor Jöns Hilborn’s research interests is long. But they all have a single objective in common: to bond molecular pieces of a jigsaw puzzle.

The fact that Jöns Hilborn, a polymer chemist, works at the Ångström Laboratory surrounded by engineers is entirely logical. In his work of designing and building chains of molecules for bone and tissue, he is a true exponent of the art of engineering. To assist him he has the cell laboratory in Sweden’s largest clean room, in the same building, and close contacts with chemists, materials scientists, biologists and physicists.
“We have several biomaterials groups that use the cell lab, which means we can compare notes and collaborate when the need arises,” Jöns Hilborn says. “One example is Håkan Engqvist’s Applied Materials Science group. This is the 12th year our two groups have been working together.”
The Ångström Laboratory will soon be extended and a new cell lab with room for even more users is planned. One of the groups Hilborn looks forward to working closely alongside is headed by Peter Lindblad, Professor of Microbial Chemistry.
“If we get a group that does protein analyses right next to us, a bioscience centre will be formed here at the Ångström. Then we can jointly, at molecular level, evaluate the molecules and materials we develop and the molecular responses we get in cells and tissues,” Jöns Hilborn says.

In the past six years, his research group has been working on biomaterials capable of steering functions in cells and tissues. These materials are based on chain-like molecules or polymers, both synthetic and natural. Natural polymers include proteins, the body’s building blocks, which are indispensable for all bodily functions and cellular processes. Another group of polymers is polysaccharides, one of which — hyaluronic acid — is used by Jöns Hilborn’s team to fabricate scaffolds for materials to regenerate bone.
“One of the researchers in my lab, Tim Bowden, has developed a kind of hyaluronic acid gel that’s anti-inflammatory and could be used, for example, to treat inflammation in the joints or gums. Molecules we find naturally in the body are incorporated into the gels and then we can steer biological responses when the materials are placed in the body.”

Gels of hyaluronic acid have proved capable of preserving and protecting proteins such as growth factors, to stimulate growth of bone or blood vessels. What is more, the group’s studies at molecular level and in cell cultures have revealed how to manufacture materials to work in vivo, i.e. inside the body. Animal tests have also been successful.
“Cells can absorb short fragments of hyaluronic acid by interacting with receptors on the cell surface,” Jöns Hilborn explains. ”Hyaluronic acid, which exists naturally in the body, easily passes the cell membrane and is degraded by enzymes inside the cell. This means that hyaluronic acid can be a useful tool for carrying active substances into cells. So we have a potential target-seeking carrier that gets right inside cells, including many tumours.”
Inserting these active substances in cells, which is known as ‘transfection’, is based on the same mechanism that viruses have developed to penetrate human cells. The goal is to be able to control the production of proteins from inside the cells using substances under development by research colleague Oommen Varghese. These substances consist of nucleic acids, which are essential components of DNA and RNA and include human genetic information.

The research group is on the track of the building blocks that, according to Jöns Hilborn, can transform medicines worldwide. Cystic fibrosis, haemophilia, cancer, Parkinson’s disease and inflammatory arthritis are just a few of the 4,000 or so diseases that could be tackled.
“We’ve found a way of designing RNA sequences that have proved to avoid degradation in the cell, have minimal side-effects and don’t stimulate the immune system. So it looks as if we’ve surmounted some of the fundamental obstacles that, to date, have been prevented new medicines from being developed. In the future, to make customised medicines by automated synthesis, it may be enough to take samples from tumours and, using a computer, determine the optimal sequence of nucleic acids,” Jöns Hilborn says.
The goal is the day when treatment for cancer involves little more than a routine visit to the health centre.
“People will be able to tell one another ‘Yesterday I had a test done that showed I’d got cancer’ and get the reaction ‘Well, you’d better go to the doctor, then.’ And the doctor can get rid of the cancer. I think that’s the future.”

Jöns Hilborn can relate personally to what this kind of breakthrough would mean. Just over two years ago he was suffering from Burkitt’s lymphoma, an extremely aggressive cancer that attacks the lymphatic system. What started with stomach troubles and feeling weak proved to be a fast-growing tumour measuring 18 cm across and weighing 3.2 kg.
“My wife told me ‘You mustn’t give that lecture in Gothenburg tomorrow — you’re going straight to the hospital,’ but I said ‘Never mind about that, I haven’t got time.’ But she insisted, so we went to the hospital and there it turned out I had stomach cancer.”
Jöns Hilborn’s tumour was of a type that doubles in volume in 24 hours. For three days, he was convinced he wouldn’t survive. But then a thoroughly pleased and relieved doctor came into the hospital room and said that thanks to its rapid growth rate, the tumour was treatable.
“Being so aggressive, that kind of tumour gobbles up masses of nutrients and oxygen,” Hilborn says. “So when you start taking the medication it goes straight to the tumour and effectively knocks it out.”

He was treated with anti-cancer drugs (chemotherapy) but had no need for radiation or surgery. His return to health was comparatively rapid, partly thanks to his being relatively young and in good physical shape. He refused to take a break from his exercise regime, either running or taking hour-long walks “while the anti-cancer drugs pumped into my body”. After five months he was able to start working again, attending meetings and even doing a bit of work in the lab.
“One side-effect of cancer treatment is mental fatigue, and I had to fight to fend it off. But today I feel fine, and I’m cancer-free. If it comes back I’ll just go into hospital and we’ll do another course of treatment. And I’ll survive that too.”
Asked what the ultimate objective of his research is, he replies promptly.
“Getting out there and being able to treat patients. I’ve had piles of work published, been out in the world giving lectures, run major projects, worked in industry, developed products — but I still haven’t helped humanity with the most serious diseases. Just think, if this cancer thing works out — then I’ll feel I’ve done what I have to do.”

Anneli Björkman

2017-01-13

Facts: Jöns Hilborn

Title: Professor of Polymer Chemistry at the Department of Chemistry, Ångström Laboratory, Uppsala University.
Age: 60.
Family: Three children aged 21, 28, and 31. Wife.
Home: Krusenberg, Ekshagarna, 15 km south of Uppsala.
Spare time: likes cross-country skiing (“I’m the sort of person who can get up at half past five in the morning, when it’s 23 degrees below zero, and ski for an hour”), canoeing in the archipelago, gardening, felling trees, chopping wood and lighting log fires in the winter.
Hidden talent: cookery, mainly spicy food.
Favourite music: good rock like AC/DC.
Want to do more if I have time: being more in the lab. Woodwork: “At our country place I’ve got a workshop with a carpenter’s bench and tools where I can do everything from carving birds from wood to building a jetty or a new house. My exam project at upper secondary school, in the Natural Science line, was making wooden sculptures — various carved wooden birds that were displayed in glass showcases at school.”