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Using Fish to Unlock Secrets of Human Diseases
June 3, 2014   
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In a new project in Poland, transparent zebrafish are being bred and used in biological and medical research by the International Institute of Molecular and Cell Biology in Warsaw.

The zebrafish—transparent fish from Asia that are several centimeters long and can be found in many home aquariums—are being used as a model organism in research into the mechanisms of certain human diseases, such as cancer, heart disease and neurodegenerative disorders.

Next to mice and rats as well as fruit flies, zebrafish have been used as a model organism by scientists internationally for years. The Warsaw scientists are conducting their research as part of FishMed, a project financed by the European Commission and the Polish Ministry of Science and Higher Education.

The most commonly used animal models are mice and rats. However, the institute did not have its own animals. In turn, using mammals for research is difficult for ethical reasons. Jacek Kužnicki, director of the International Institute of Molecular and Cell Biology and head of the FishMed project, proposed using a new research model—zebrafish.

The institute’s aquariums hold some 6,000 colorful zebrafish at various stages of development. They require time-consuming maintenance procedures, including monitoring the water and regular feeding.

Zebrafish embryos during the first few days of their life are almost transparent—scientists can see individual cells within the body of the fish, which enables observations of processes occurring inside their bodies.

“The zebrafish has traits that make it possible to carry out certain tests faster and more cheaply,” said Kužnicki. “These can help us understand the mechanisms of some human diseases. One of these traits is that in the early stages of development zebrafish are completely transparent, allowing us to observe cells that divide and shift as they develop.”

An additional advantage of using such fish for research is that it is possible to obtain a huge number of 2- to 3-day-old embryos—and thus test, within a few months, tens of thousands of different chemical compounds as potential drugs. This decreases research costs.

In addition, fish are genetically close to man. Some 70 percent of their genes are identical and 90 percent are similar, according to researchers. If scientists identify a mutation in the human gene, it is likely that the same gene can be found and mutated in zebrafish. This can help solve many puzzles linked to human genetic diseases.

Almost every human disease can be studied in the fish through appropriate manipulation. Researchers are able to mutate a specific fish gene that has a human counterpart and that they know is the cause of a disease in humans. Then they observe the pathological changes as the zebrafish develop.

Kužnicki is collaborating with Prof. Oliver Bandmann, a physician and scientist from the British city of Sheffield, who has created a fish model of familial Parkinson’s disease. This model involves fish with a mutated gene called pink-1. Using this model, Bandmann has traced the slow disappearance of neurons that produce dopamine in the fish. This is exactly the same mechanism that causes the progression of Parkinson’s disease in humans. When 80 percent of such neurons disappear in a specific part of the human brain, Parkinson’s disease appears. The course of these pathological changes can be traced using the zebrafish. Scientists are looking for ways to prevent the progression of the disease. They are dissolving different substances in water and checking if they can stop or at least delay the disappearance of the dopaminergic neurons. For many years, no new drugs have been developed for Parkinson’s disease. With time patients must increase their doses of the drug, but after some time it stops working.

Zebrafish are also helpful in research into cancer drugs. A team led by Prof. Maciej Ŋylicz is working with Prof. Ewa Snaar-Jagalska, of Leiden University in the Netherlands, who has demonstrated that it is possible to transplant prostate cancer cells in fish and observe the development of this cancer. Activation or inhibition of selected genes makes it possible to understand the causes for the development of this disease. Moreover, using such a model, scientists are looking for ways to inhibit the cancer process by testing different chemical compounds, administering them to the water in which the fish live.

According to Snaar-Jagalska, research is made easier by the fact that zebrafish reproduce fast. The development of an embryo into adult zebrafish takes three months, and a single pair of fish produce up to 300 embryos a week. “This is a tremendous amount of genetic material,” Snaar-Jagalska said, adding that the development of the embryo takes place outside the mother’s body, allowing the observation of the organism at any stage of its development.

Compared with mammals, the introduction of genetic modification in fish is simpler and faster. According to Kužnicki, modifications can be introduced into the fish genome that can make a particular type of cell glow, making observations of these cells easier.

However, these studies are still a long way from practical application. Every tumor is different. And even in the same patient different parts of the tumor often behave differently. Nevertheless, this type of research brings scientists closer to better understanding the process of tumor formation and to identifying ways of combating cancer. The currently available anti-cancer drugs are the outcome of similar experiments. Research conducted with the participation of Snaar-Jagalska has helped identify two new genes that are involved in the development of prostate cancer. This marks significant progress in understanding the mechanism of its development.

The fish model can also be used for research into various infections.

According to Kužnicki, zebrafish breeding will not eliminate research using mice and rats. “By using zebrafish, however, we can significantly reduce the use of mammals in research,” Kužnicki said.

Karolina Olszewska
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