Animals in Cancer Research

It is often unfeasible to study cancers directly in humans, and it is certainly unethical to induce them in humans for the purposes of research. Consequently, researchers often study cancers in model organisms such as mice, fruitflies or zebrafish, in the hope that insights might be later applied to humans. This is possible because many fundamental biological processes are shared by all life on earth, so model organisms don't necessarily have to be mammals or visually similar to humans.

One place in which such research takes place is at the Walter & Eliza Hall Institute (WEHI) in Melbourne, Australia.

How is cancer induced in a zebrafish?

The process for producing zebrafish with a particular cancer-causing mutation is as follows:

  1. Expose male fish to to a chemical mutagen, N-ethyl-N-nitrosourea, which is more commonly known as ENU. (ENU is a highly potent mutagen that is also used in mice.) This will induce mutations in the sperm of those fish.

  2. Allow those males to mate as per normal. The resulting clutches will have inherited some of the mutations from their fathers.

  3. Observe the development of the offspring and single out those fish that possess the mutation or phenotype you would like to study.

  4. Selectively breed those fish to more consistently produce model organisms with the desired mutation.

What are the advantages of using zebrafish?

As outlined in the above video, there are several advantages to using zebrafish as a model organism.

  • Their external fertilisation and transparent embryos allow developmental processes to be directly observed.

  • A comparatively short gestation & maturation period permits a greater speed of experimentation.

  • Because they are small and sociable they can be housed densely, so are affordable to maintain in large quantities.

  • Their large clutch size means that it is easy to produce many organisms with the desired mutation.

  • It is easy to induce mutations using common chemical mutagens.

  • Importantly, they are genetically similar to humans. 85% of zebrafish genes have counterparts in humans, and nearly all human genes that predispose to cancer in humans are present in zebrafish.

Of course, there are some inherent limitations in using a fish to model human disease. The lack of lungs or mammary glands mean that zebrafish cannot be used to model lung or breast cancers, for instance.

How might the use of zebrafish lead to new cancer treatments?

The use of zebrafish brings many advantages to studying cancer. Recent research has focused on the use of fluorescence imaging to study the development of zebrafish embryos.

Fluorescence is a powerful imaging technique in which "dyes" (or commonly used fluorescent proteins, e.g. green fluorescent protein - GFP, as seen in the video), are used to create a 3D rendering of an object of interest. The object of interest in the video happens to be the small intestine.

Recent fluorescence imaging techniques have become even more powerful, and with the assistance of computers, fluorescence imaging now allows researchers to image single particles. Therefore, it is possible to track the development of the small intestine in real-time.

In the context of cancer, researchers have discovered that blocking certain developmental pathways of the small intestine inhibits tumour growth, or in some cases, "kill off cancer."

From here, the next challenge is to identify or create drugs/compounds that can block developmental pathways and perhaps inhibit tumour growth. Most research labs and pharmaceutical companies have in their possession very large chemical libraries (sometimes containing over one hundred thousand compounds) that can be screened for efficacy in inhibiting tumour growth. After one, or a few, compounds with potential anti-cancer properties have been selected, the compounds undergo further development and then clinical trials for use as future anti-cancer therapies.

Is it ethical to use animals in medical research?

This is an open question. Each year, hundreds of millions of animals are used and killed in experiments. Many of them are subjected to severe pain or given debilitating diseases so that they may be studied. On the other hand, animal research has contributed to 70% of the Nobel prizes for physiology or medicine. Furthermore, findings from animal research have helped to extend or improve the quality of life of millions of people. Some of these findings have helped the development of various vaccines, blood transfusions, asthma inhalers and kidney transplants. In many cases the research can be carried out with minimal suffering on the behalf of the animal. Here is one researcher's experience.

The work we do is performed with compassion, care, humanity and humility. All my rabbits, when I worked with them years ago, were stroked and petted every day. ... My genetically modified rodents breed happily, and their offspring are indistinguishable from those of other rats and mice. Medical researchers are compassionate people seeking to alleviate pain and suffering. They are unlikely to do anything that is unnecessary or cruel. Indeed, they are not allowed to, because of the rigour with which animal licences are granted by government.Professor Robert Winston

That said, this is not representative of every situation, and there is always a trade-off to be made between the welfare of laboratory animals and the welfare of humans who might benefit from the advances that result from the research.

An extensive summary of the medical advances that have been made possible through the use of animal research can be found in this pdf.

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