By Jack Gordon
I am a second year Biomedical Science student here at the University of Sheffield. I am fascinated by molecular biology and I am currently taking an anatomy module which involves human dissection in the Medical Teaching Unit (flushing out intestines is something I am glad to have ticked off my bucket list). For my first post I thought I would tackle a topic which sparks a fair deal of controversy; animal research. I remember my first lectures at University feeling like Zoology. Learning all the different life cycles and structures of fruit flies, zebrafish, mice, sea urchins, worms and frogs was certainly not what I was expecting. In later lectures, we were introduced to all the diseases caused by mutations in genes shared between those species and our species; my scepticism was gone.
Initially I was not convinced that animal research could be translated to humans – especially research involving organisms which diverged in from humans hundreds of millions of years ago in evolution such as Drosophila Melanogaster (known as the Fruit Fly to mere mortals). Yet, this ‘simple’ organism has yielded 6 Nobel Prizes in Physiology and Medicine, the latest coming just this month for research looking at the body’s internal clock. The question is: why can we learn so much about human physiology, disease and even behaviour from animal studies?
The answer – as you might expect – centres around evolution and the genes shared between species. DNA is universal – which means it is found in all living organisms (some viruses do have RNA genomes but are they alive?) – and it is this fact that means you hear all kinds of claims when it comes to how much of the human genome is shared with different animals and even bananas. It is clear that many genes have been conserved across hundreds of millions of years of evolution – we can inject human DNA into animal cells and watch them synthesise the protein that the gene encodes. Genes are conserved because they are good at their jobs, for example Hox genes which establish the ‘body plan’ in the embryo (essentially telling which part to become head and which legs etc) are found in humans and many other species including Drosophila. Mutations in Hox genes are associated with a number of human diseases and therefore, by intentionally mutating these genes in animal models we can study the disease and conduct drug screens to find candidate drugs for clinical trials. In the case of Drosophila, they are ideal research subjects; they reach sexual maturity in 8 days, can be kept in large numbers easily in the lab and only have 4 pairs of chromosomes (compared to 23 pairs in humans). Much of Drosophila research involves identifying and characterising important genes in diseases, a whopping 714 Drosophila genes are associated with human diseases such as the CFTR gene that causes Cystic Fibrosis or neurexins thought to be associated with autism.
Because animals have many of the same genes as humans, known as homologs, their cells are doing many of the same activities our cells are like synthesising proteins, replicating DNA and undergoing divisions. So, our cells are doing the same things but does this matter? Does it translate to therapies that improve treatment for patients?
If we take cancer as an example, HER2 is a gene which, when mutated, causes an aggressive form of breast cancer. We are able to screen tumours for HER2 amplification using fluorescent imaging techniques and it is found in around 30% of all breast cancers. HER2 was first identified through research with mice and, perhaps more amazingly, the treatment for this cancer is a humanised form of an antibody isolated and cloned from mice. Herceptin was one of the first so called ‘personalised treatments’ and was hastily christened a wonder drug by the media. This is just one example of animal research leading to treatments, there are hundreds more and all drugs must demonstrate efficacy in animal models before receiving the green light for ‘first in human’ studies.
Some people are willing to predict that animal research will decline due to the emergence of organoids – 3D structures composed of human cells- such as mini-brains. While these advances offer massive opportunities, I feel animal research is here to stay, and we are all better off because of it.