Fewer and better animal experiments best for all

ECOTOXICOLOGIST MALIN CELANDER and her research group are studying the effects of different chemicals on fish. During her doctoral studies and subsequently, she has used many fish in animal experiments to achieve reliable results in her research.
“We look at how the fish’s liver reacts to added chemicals and, in particular, what happens when the fish are exposed to several chemicals at the same time. This can cause harmful combination effects, which means that the limit values for the chemicals individually are not sufficient to limit their environmental damage,” says Malin Celander.

Today, much of her research has moved into the cell culture lab four floors above the aquarium installation at Medicinareberget. Here, her research group are using cultured cell lines from the liver of a guppy species to test the toxicity of chemicals. Malin Celander’s research group are focusing on aromatic hydrocarbons from exhaust gases anddrugs to treat fungal infections.
“The cell lines keep dividing continuously and stably. We add different chemicals to the cells in varying concentrations and blends. This allows us to identify both the critical concentrations of the chemicals and the critical points in time of their impact. We can then reduce the number of experiments we need to carry out on live fish.”

THE METHOD REDUCES the number of laboratory animals needed, but not to zero. Fish are complex organisms and when there is a reaction in their livers, it can cause reations in other organs. This cannot be detected in the cultured liver cells.
“The biggest benefit is that we can screen chemicals more broadly so that we have a better chance of guessing what is happening in the fish’s liver. We can then analyse the effects in the cells over time to see if, and when, a combination effect arises.”

MALIN CELANDER ALSO collaborates with mathematicians in her research, as it is not ethically or practically possible to test all combinations of chemical blends. Using data from previous research, the mathematicians have identified 10 parameters in 17 equations that describe the impact on fish liver cells when two chemicals are blended. This new model also illustrates how the concentrations of the chemicals in the cells vary over time.
“The mathematical model identifies which blends of chemicals can create unwanted combination effects. Then we can test the mathematical model in animal experiments. But by that time we have a better idea of which concentrations and which blends to test and at what point we need to euthanise the fish to detect the impact on their liver and thus reduce the number of laboratory animals used,” says
Malin Celander.

but not even cell culture is entirely free of animals products. Calf serum from unborn calves is often used as a culture medium in animal cell culture. With researchers in the UK, Malin Celander is developing methods to replace calf serum with a synthetic serum. So far, they have managed to reduce the volume of calf serum by 75 per cent.

ALL RESEARCH INVOLVING animal experiments is regulated in Sweden’s law. The long-term goal is to minimise animal experiments
without adversely affecting research. Researchers must show that the experiments are carried out with the least possible suffering for the animals and that alternatives have been explored.

Professor Michael Axelsson is the supervisor responsible for animal experiments at Zoologen, one of three laboratory animal facilities at the Faculty of Science.
“I don’t think the legislation has made research more difficult, but it has improved the situation for laboratory animals. More research can be done using cell cultures now than previously, and it’s now becoming possible to study how multiple cells react to different factors at the same time,” says Michael Axelsson.
“We are also working on developing less invasive experiment methods. To measure a fish’s brain activity, researchers have designed a suction cup that is attached to the fish’s head. Surgical intervention is no longer needed, and the suction cup can be easily removed,” says
Michael Axelsson.

THE FACULTY OF SCIENCE’ S research uses a variety of animal species such as zebrafish, rainbow trout, bull-rout, gobies, hagfish, sticklebacks and lizards. New areas of research in the future may require other species. The ethical aspect of animal experiments is not the only one. There is also the financial aspect.
“Purchasing laboratory animals is one thing. The expensive part is keeping them in an environment which is good for our research and good for the animals. We have access to vets and the animals are
monitored 24/7,” says Michael Axelsson.

Text: Olof Lönnehed
pHoto: Dick Gillberg, Malin Arnesson