Models in research

A lot of research (especially in biological sciences) is conducted using ‘models’. Like models in the fashion world, research models serve as a showcase of a specific (trait) or phenomena and can be a very useful tool for those scientists who are interested in that problem.

Some models used in biological research include the common mouse, Mus musculus, the zebrafish, Danio rerio, the African claw toed frog, Xenopus laevis (in the news recently as the potential bad guy involved in the spread of the chytrid fungus), and the fruit fly, Drosophila melanogaster. A great deal of research has been performed using these species, and we now know a great deal about their lives from egg to adult. Some research uses these species, and the fact we know a lot about their physiology, their behaviour, and their molecular biology to ‘model’ what happens in other organisms(1), especially humans. This is an amazing consequence of the evolutionary relationships between all animals and plants on Earth, that so much of our biology is shared with something as seemingly unrelated as a fruit fly and has lead to large improvements in human medicine in particular.

Sometimes researchers use specific cells from an organism to ‘model’ a particular biological phenomenon in that organism. This is often the case in the study of cancer, with model cell ‘lines’ being the subject of research for many labs.
However, like fashion models, research models aren’t perfect. Cancer research is one particular field using models that is becoming complicated by the recent advances cancer research and the understanding that cancer may not be a uniform disease. One famous cell used in the study of cancer is the HeLa cell, a cell type taken from a tumour of a patient years ago and used in labs throughout the world. Studies on the HeLa cell have contributed significantly to our understanding of human disease, even helping in the creation of the polio vaccine, but recent research may now suggest it’s time as a model is coming to an end.

With the advances made in biotechnologies, it is now almost trivial to sequence the entire genome of non-model organisms, or even specific cell lines, to gain a greater understanding of their cell and molecular biology, eliminating at least one of the benefits of using models in research. Last month, the genome of the cancer cell line, HeLa, was sequenced and decoded, and researchers found a multitude of errors, questioning its usefulness for the study of cancer in the 21st century. Among these errors are duplications in the number of chromosomes, number of copies of genes, and expression of those genes relative to other human cell lines. It is unknown whether these errors were present in the original tumour(2) (and possibly contributing to the development of that tumour) or if they have accumulated during their life in labs all over the world.

Tumour biopsies for successful development of cell lines for research aren’t trivial, but given the uncertainty over HeLa’s history and the increasing ease of access to sequencing technology, may be the only way to continue research into cancer.

(1) Developmental biology (the process of transforming from a fertilised egg to an adult) has gained a lot of understanding from the use of these models and applying it to closely related species. However it doesn’t always work: for example, Drosophila melanogaster undergo a very precise development pathway involving a stripe patterning of the early embryo with the expression of certain genes called Hox genes. Whilst this is similar to many animals, and Hox genes are very important in development, the specifics of the method in Drosophila are not shared even within all the Arthropods – some spiders use a different Hox patterning for their body.
(2) An excellent article from Genomics Adventures discusses the ethics of publishing the HELA genome. As scientists we should never forget the people behind our studies and this article reminds us of our duty.

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2 thoughts on “Models in research”

  1. Great article! Having worked with Mus musculus, Schizosaccharomyces pombe, Sacharromyces cerevisiae, Caenorhabditis elegans, and Drosophila melanogaster, I am a firm proponent of using model systems to understand basic biological problems. Yup, they ain’t perfect, but when you use one to cross-validate results in the other, you can get a general idea about conserved mechanisms. I think you’d agree, no?

    Thanks for throwing this up!

  2. That’s a long list of organisms! What are you currently working on? I went to a talk last night that reminded me how great Drosophila is – all down to evolution!

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