Words by Isabel O'Brien
The pharmaceutical industry has been trying to refine, reduce and replace animal testing for some time, but animal rights activists argue progress is too incremental. Gains have been made, but what is the activists’ case for acceleration?
If you were to thrust animal rights activists into a room with pharmaceutical researchers, you’d expect a few sparks to fly. According to the European Federation of Pharmaceutical Industries and Associations (EFPIA), the pharma industry’s use of animals in scientific research has nearly halved during the last decade, but activists are keen to see progress accelerate and become more comprehensive.
“The industry has always seen the welfare of animals as crucial to good science,” argues Kirsty Reid, Director, Science Policy, EFPIA. But this perception is not necessarily widely accepted or understood, as Jarrod Bailey, Science Director, Animal Free Research UK, caveats: “The pharmaceutical industry’s efforts in response to this have always appeared mixed and quite contradictory.”
Overall, both groups are in agreement that animals do not deserve to suffer for the benefit of human health, but where one side is primarily looking at ways to make trials more humane, the other has a razor-sharp focus on eradication.
Refine, reduce, replace
The ‘Three Rs’ are where the crux of the conflict lies. Standing for ‘refine, reduce and replace’, activists accept the pharma industry is becoming adept at refining and reducing animal testing, but argue it is struggling to truly make gains in replacing the practice entirely.
“There have been positive, constructive conversations with individuals over the years who’ve been supportive of the Three Rs at the very least, or even replacement altogether,” says Bailey. “But on a more macro level, there have been corporate messaging and position statements that are consistently defensive of animal testing.”
The industry has always seen the welfare of animals as crucial to good science
EFPIA’s latest report on the industry’s progress is far from defensive, but it certainly focuses on steps to refine and reduce animal testing rather than replacement. For example, the analysis recounts the ways in which researchers can adapt animals living quarters to be more comfortable and stimulating, as well as examples of new technologies that can reduce the number of invasive procedures required to take samples.
“They may have mitigated some animal suffering at times, but they have also failed to significantly tackle – or may well even have exacerbated – the use of animals in drug development,” critiques Bailey. “This is because pursuing the Three Rs – unless there is a specific effort on replacement – tacitly accepts the premise of using animals and their role as accurate and reliable ‘models’ for human biology.”
In response to the criticism of the Three Rs, EFPIA has revealed a new philosophy it’s using to shape its strategy. Published in 2021 by philosophers David DeGrazia and Tom Beauchamp, ‘The Principles of Animal Research’ has been described as more comprehensive than the Three R methodology, especially as “they consider responsibility for the wellbeing and quality of life of the individual animal”, Reid explains. The six principles encourage researchers to weigh up the individual suffering of an animal against the expected net benefit.
Is animal testing effective?
Think of animal testing and its ethics will be the first aspect to jump to mind. Animals are ultimately unable to consent to being enrolled in a trial like humans can, but there is another key motivator driving efforts by activists and researchers to find alternatives.
“The reasons the pharmaceutical industry works towards limiting using animals, go beyond being ethically motivated,” explains Reid. “It is also due to an increase in new and evolving technologies, innovations and predictable methods, which, on one hand, aid in eliminating animal suffering and use, and on the other, provide better and more reliable data than animals.”
What matters for all concerned is that this change happens, and that it happens as quickly as possible
This is an area in which researchers and activists are aligned – to a point. Both sides are in agreement that animal responses do not perfectly replicate human responses, but while the pharma industry still views tests as highly scientifically relevant, activists such as Bailey believe “the evidential weight provided by animal tests of new human drugs is hugely insignificant”. He argues that “this is largely due to species differences in gene complement and gene expression, notably in genes and enzymes involved in xenobiotic metabolism”. The evidence of animal data being compromised by the stress experienced during procedures is also of note, he adds.
While the pharma industry accepts the distinct genetic and enzymatic differences between humans and animals, it is restricted by the fact technology has not yet reached the right level of sophistication to be used as a substitute.
“Applying alternative methods may lead to significant reduction in animals used, however most of these methods are not yet able to fully replicate the complexity and reactions of a living organism, especially for systemic and chronic conditions,” admits Reid. Clearly, increased investment must be allocated to developing superior models, and the financial returns could be substantial, too.
This was demonstrated by a recent liver-on-a-chip approach in humans that was able to predict drug induced liver injury, which is “a major single cause of drug failures in clinical trials – much better than poorly predictive animal test”, reveals Bailey. He says in vitro solutions like this, which allow researchers to replicate the function of tissues and organs and bridge the gap between animals and human systems, could save the pharma industry up to $3bn per year. Not a figure to be sniffed at for certain.
But for now, the pharma industry’s focus is on reducing the number of redundant tests to the bare minimum required to protect public health. Developing analytical methods to replace animal testing is also a priority, but less advanced. Does this approach cut the mustard for animal right activists? No, but as Bailey notes: “What matters for all concerned is that this change happens, and that it happens as quickly as possible.”
This article features in GOLD 24 – read the full issue here.
EFPIA members are committed to the science-based phase-in of methods to replace the use of animals for scientific purposes and the deletion of animal tests which are obsolete or redundant.