30 Aug 2024

Research blog: Balancing Act

Leukaemia is a complex disease that affects about 490,000 people worldwide.(i) Despite decades of research, the exact causes and most effective treatments for various types of leukaemia remain elusive. One critical but controversial tool in the fight against leukaemia is the use of animal models. While this method has played a significant role in advancing our understanding and treatment of leukaemia, it also raises ethical questions that cannot be ignored.

The role of animal models in leukaemia research

From Dr Lloyd Law’s pioneering research in the 1940s and 1950s on the response of murine (mouse) lymphoid leukemias to antimetabolite agents to Dr John Dick’s discovery of the leukemic stem cell in the 1990s, animal models have been essential to our understanding of leukaemia biology.(ii) Major breakthroughs in blood cancer research and the development of new treatments — such as understanding the mechanisms of disease progression and developing the foundations for chemotherapy and stem cell transplants — have relied on animal research.

But why are animals so important in leukaemia research?

One major factor is that leukaemia is not a solid cancer; it involves the blood. Not only does this flow through the body meaning there is no chance of removal by surgery like many other cancers. But also, leukemic stem cells start in the bone marrow – the place of origin and key to targeting.(iii) The bone marrow is an extremely difficult environment to replicate in the lab, making animal models essential for such research. Animal models allow scientists to observe how medications affect both the cancer and the body as a whole, providing insights that are difficult to achieve through other means. For example, the development of chemotherapy, which has become a cornerstone of leukaemia treatment, relied heavily on animal studies. These studies have also been crucial in understanding the side effects and optimal dosages of these powerful drugs, helping to create more targeted treatments with fewer side effects, such as tyrosine kinase inhibitors for chronic myeloid leukaemia (CML), which have dramatically improved survival rates and quality of life for patients.

Despite the unique challenges that blood cancers like leukaemia present in treatment and research — primarily due to not being solid tumours — they are not the only cancer or research area finding necessity in animal research. In fact, it’s a legal requirement that all potential new medicines intended for human use are tested in two species of mammals before they can be given to human volunteers in clinical trials.(iv) This is partly because animals are biologically very similar to us. For example, mice share over 98% of their DNA with humans(v) and can develop many of the same health issues, like cancer, diabetes, and heart disease. Plus, their shorter life cycles let researchers study diseases over their entire lifespan and across multiple generations, giving crucial insights into how diseases work in living systems.
Animal testing has played a key role in the development of countless life-saving treatments. But its role extends beyond critical care; many everyday medications, such as paracetamol(vi) and progesterone(vii) (used in birth control), have also undergone animal testing before reaching your medicine cabinet.

The Ethical Dilemma

While the contributions of animal testing to medical research are undeniable, they come with significant ethical questions. The use of animals in research raises questions about the morality of causing potential suffering to living beings in the pursuit of human health benefits. Some argue that the lives of animals are just as valuable as human lives and that subjecting them to painful or distressing experiments is unjustifiable, even in the name of scientific progress.
Moreover, there is ongoing debate about the effectiveness of animal testing in truly replicating human responses to diseases and treatments. Critics point out that many drugs that pass animal testing phases fail in human trials, suggesting that animal models are not always reliable predictors of human outcomes. Which is to be expected as they are, of course, not humans. But animal models are the most reliable tool available to us to test whether a medication has significant side effects without putting humans into unknown risk.

Striking a Balance
The challenge lies in striking a balance between the undeniable benefits of animal testing in medical research and the ethical imperative to reduce harm. The scientific community is very aware of these ethical concerns and is actively seeking alternatives to animal testing. Advances in technology, such as growing organ systems in a lab and computer modelling, are providing new ways to study cancers without relying on animals. These methods can potentially mimic human biology more accurately, leading to more effective treatments and making animal experimentation less important. In addition, there are very strict regulations and ethical guidelines that govern the use of animals in research, making the UK a leader in standards. Researchers are required to follow the “3Rs” principle—Replace, Reduce, and Refine. This means that they must seek alternatives to animal testing wherever possible, minimise the number of animals used, and refine their methods to cause the least amount of suffering. Additionally, the application process is lengthy and involves applying for more than 3 separate licenses to the Home Office and numerous facility inspections.

Conclusion
Animal research has been, and continues to be, a vital tool in studying leukaemia, contributing to many of the treatments that save lives today. However, it also presents significant ethical challenges that cannot be ignored. As science progresses, the hope is that we can continue to find innovative ways to study leukaemia that reduce or eliminate the need for animal testing altogether.

In the end, understanding and curing leukaemia is a balancing act—one that requires us to weigh the benefits of scientific advancement against our responsibility to treat all living beings with compassion and respect. The future of leukaemia research really depends on how well we can navigate this tricky terrain, aiming for breakthroughs that are not only effective but also ethically sound. At Leukaemia UK, this is something we’re deeply committed to. A lot of the research projects we fund don’t involve animals at all. When we do fund studies that include animal research, it’s only because there’s no other option, and we ensure they fully comply with the Animals (Scientific Procedures) Act 1986 and the guiding principles of the 3Rs.

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References:

(i) Novotech: Acute Myeloid Leukaemia – Global Clinical Trial Landscape (2024), March 7, 2024, The report contains a comprehensive table of treatment therapies and when they should be administered / dosage and how aggressive the treatment is. Accessed 08/08/2024

(ii) Cook GJ, Pardee TS. Animal models of leukaemia: any closer to the real thing? Cancer Metastasis Rev. 2013 Jun;32(1-2):63-76. doi: 10.1007/s10555-012-9405-5. PMID: 23081702; PMCID: PMC3568447.

(iii) American Cancer Society. (2021). How Is Leukemia Diagnosed? Retrieved from https://www.cancer.org/cancer/leukemia/detection-diagnosis-staging/how-diagnosed.html

(iv) chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.understandinganimalresearch.org.uk/application/files/8016/5226/6721/Animal_research_The_facts.pdf
Animal Research: The Facts. Understanding Animal Research. Accessed 14/08/2024

(v) https://med.stanford.edu/animalresearch/why-animal-research.html Accessed 14/08/2024

(vi) https://www.ed.ac.uk/research-innovation/animal-research/news/paracetamol-study-sheds-light-on-liver-damage Accessed 09/08/2024

(vii) https://www.ivis.org/library/recent-advances-small-animal-reproduction/clinical-use-of-progestins-bitches-and-queens-a-0 Accessed 09/08/2024