1 year ago
23 February, 2023
That injustice was and remains animal experimentation. The more I learned about it, the more I felt it was ethically wrong. Certainly, we should not inflict pain, suffering and death on sensitive beings for any reason. But on top of that, there was a burgeoning epiphany that it was poor science.
I increasingly shared a view with many other scientists that science could and should be doing better. I held a conviction that research into human diseases should move away from futile attempts to translate data from animals to humans and focus instead on the species at hand. Only by conducting research with a uniquely human perspective could we hope to understand human biology and disease and find new and effective therapies for them.
And so, this shift in how research should be conducted is a human ethical issue as well as an animal one. If we use research methods that confound instead of inform, particularly when better approaches exist, we are letting down billions of people and patients.
I set about building on the evidence base that is needed to change this. Evidence was already out there, but it was being ignored; there wasn’t enough. Some 200 million animals every year are used globally in science. Around 3 million in the UK alone.
In the UK, we are where we were for much of the past four decades and even as far back as the 1960s. This is not just in terms of how many animals we use in science but also in what we know about many diseases and what we can do to treat them. Those billions of animals’ lives have delivered nowhere near enough useful data, and it can be soundly argued that much progress has been made despite their use rather than because of it.
In short, I (and many other scientists) believe that the human relevance of animal research is so poor we simply have to do something else. Crucially, that ‘something else’ has never been more exciting, promising and capable than it is currently.
With specific regard to cancer, all the above appears to be especially true. We know that predicting the risk of cancer from exposure to certain chemicals, which can account for up to 20% of all cancers, cannot be predicted reliably from animal tests. The ‘general’ nature of tests using animals cannot translate to specific types of cancer, including the four most prevalent types, one of which is breast cancer (1-8).
We also know that relying on animals to understand what is going on in cancers and to identify and test new drugs isn’t working well at all. The failure rate of new drugs generally, over time, in human clinical trials is more than 92%. For anti-cancer drugs specifically, the rate is even higher at around 96%.
In other words, fewer than 4 in every 100 anti-cancer drugs that appear safe and effective in animal tests go on to be licensed for use in people – mostly due to unforeseen issues with safety and efficacy (9-10).
In short, to tackle cancer from all sides – preventive and therapeutic – we need to move away from using animals and focus on human biology from start to finish. Meetings of scientists to discuss what should be done have highlighted overly defensive attitudes to animal use, overly critical attitudes to using human-specific methods, issues with requirements to ‘prove’ findings in humans and human tissues in animals, and more. Yet, amazing, positive and hugely encouraging progress is being made.
In cancer research generally, as well as for breast cancer specifically, human-focused methods are paying dividends. The analysis of biomarkers, biological molecules found in the body’s tissues and fluids, helps to predict if new chemicals could cause cancers, including those of the breast (8). As do various methods using cultured human cells and analysis of the activity of their genes (11-12).
In research into cancer itself, there is growing and substantial evidence that using new 3-dimensional cultures of human cells is vastly superior to the 2-dimensional cultures used historically. 3D breast cancer cells have been shown to be more relevant in the screening of potentially effective drugs for the disease (13). For example, by more effectively modelling the responses of breast tumours to chemotherapy drugs targeting HER2, a gene that has increased activity in one-third of breast cancers, – researchers were able to offer a more effective drug treatment for HER positive breast cancer (14).
3D cultures more accurately model the environments around tumours and the interactions between tumour cells and immune cells. They more accurately model how cells function in human bodies, how changes occur around tumours and more accurately predict a new drug’s safety and efficacy in humans. This is very important because the ‘tumour microenvironment’ differs between species—notably between animals used in research and humans.
Animal Free Research UK, in collaboration with BCUK, funded human-relevant research into this specific area of breast cancer research. Our work examined the effects of certain chemicals we encounter in the environment, known as endocrine disruptors, on the risk of developing breast cancer. All use advanced, human-relevant 3D models. For more details about this work, see here.
We also supported researchers at Aberdeen University to grow cells from breast cancer patients on plastic chips, each equipped with their own blood supply, enabling the study of cells and molecules in the human tumour microenvironment in real time, closely mimicking what happens in people. The researchers have genetically manipulated these cultures to investigate which genes might control angiogenesis (the development of new blood vessels) in breast tumours. This offers new and important insights into potential new drugs to block tumour angiogenesis.
Breast cancer metastasis (‘spreading’ to other parts of the body) and dormancy (where small tumours remain dormant for years before starting to grow again) are being studied in cultures of human liver cells seeded with cancer cells. The blood supply to breast tumours, and the action of potential new drugs for breast cancer, are being investigated in ‘organ on a chip’ approaches. This is where human tumours with physical and functional characteristics of actual human tumours in individual patients are modelled on small ‘chips’ with circulatory systems which help mimic human physiological environments (15-17).
Crucially, human-specific 3D models and organ-on-a-chip approaches are facilitating research that is significantly more relevant to the human disease than animal methods, as well as being humane. But they are also enabling and accelerating ‘personalised medicine’—the study of patient-specific diseases, treatments, and human variation. Scientists take small samples of blood or skin from patients and reprogram cells in those samples to be stem cells, which are then turned into specific types of cells for research that are specific to the donor’s biology.
All of this could have a huge impact on saving lives from cancer and ending animal suffering. In the UK alone, around 55,000 women every year are affected by breast cancer, and it is estimated that more than 4,000 animals are used and die directly in laboratory experiments associated with breast cancer (not including breeding). The future is already here: forward-looking research funders and scientists are embracing it, and we all stand to benefit.
For more information about me, Animal Free Research UK and everything discussed in this blog, you can listen to our podcasts.
Dr Jarrod Bailey – Science Director, Animal Free Research UK
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