Release the Beast

Like most people, I have friends and family who have suffered – or are suffering – from a common condition for which there is no known cure. Given that we are so technologically advanced – we can send people into space for months at a time! – why have we been unable to make significant inroads into our most common diseases? Why are there so few options for people with stroke and Alzheimer’s disease (AD)? Why, for some cancers, are we still using the same toxic drugs we used 50 years ago? 

At the beginning of her career in the 1970s, Azra Raza, from the Herbert Irving Comprehensive Cancer Center at Columbia University, treated acute myeloid leukemia patients with a toxic combination of drugs known as “7+3.” All she has to offer them today is the same noxious cocktail (1).

What went wrong? Why are the billions of dollars we pour into research not coming up with the goods? Well, let me share the argument I set out in Rat Trap: The Capture of Medicine by Animal Research - and How to Break Free (2). In short, I believe that much of the problem can be blamed on our reliance on animal models. Experiments on animals are justified on the basis that they produce benefits for humans, but can we honestly say – after decades of research using animal models of human diseases – that we have really benefited? 

Of course, there are cases in which animal use has been associated with medical progress, but surely a successful paradigm needs to get it right reliably and consistently. We often hear that 90 percent of drugs tested for safety and efficacy in animals go on to fail when tested in humans. But in some areas, the failure rate is even higher (it’s closer to 100 percent for stroke and AD, while for traumatic brain injury it is 100 percent) (3) – and that’s after 70 years of trying (4). Animal models are simply not good at generating effective drugs for humans. Nor are animal tests able to reliably ensure the safety of medicine. If a test shows that a drug is not toxic in an animal, there is no guarantee that the results will be reflected in humans (5).

As 2022 drew to a close, President Biden signed into law the FDA Modernization Act, replacing a 1938 Act that mandated that all new drugs be tested on animals. In other words, the FDA is now able to consider data obtained from a wide range of research methodologies, including human cell-based approaches, such as organoids and organs-on-a-chip, in silico modeling, and AI. The new law doesn’t ban the use of animals, but it does recognize the limitations of relying on them in drug discovery and development. Organ chips can outperform animal tests in detecting drugs that will be toxic to humans (6), and experts claim they are capable of doing things that animal models have never been – and never will be – able to do (7). US companies now have the freedom to choose whatever method they consider most scientifically appropriate when developing and testing their new drugs.

Biotech companies working on human cell-based approaches, such as organ chips, claim that they’re ready for the increased demand and greater scrutiny that will surely follow. Market research conducted by Axol Bioscience in 2023 indicates that 75 percent of respondents to a survey have increased their investment in cell-based research, while 34 percent have actively reduced their use of animal models, with over half citing the new Act as a key driver for this transition (8). Sanofi, for one, aims to reduce its reliance on live animals by 50 percent between 2020 and 2030 (9).

Now that the US regulator has acted, perhaps others, such as the EMA, will follow suit. There is certainly a great desire for change within Europe. In 2021, the European Parliament voted by a staggering 667:4 in favor of an EU-wide plan to phase out the use of animals in experiments. But if regulators don’t take the hint, perhaps shareholders will force change. Whether motivated by a desire to invest in ethical companies or companies that deliver greater profits, shareholders will find much to interest them in biotech companies that are developing human biology-based approaches. Such companies, by focusing on technologies that are directly relevant to humans, are likely to provide benefits to patients, improve public health, avoid harm to animals, and deliver larger dividends to shareholders. 

The compound annual growth rate for the non-animal testing market is predicted to be higher than for the animal model market over the next decade, with the former expected to expand, offering lucrative opportunities for investors (10, 11). Australia is aiming to get on board, foreseeing significant economic opportunities emerging from the development of complex in vitro models (12). In a major new report, its National Science Agency outlines the advantages of a transition to non-animal approaches, including enhanced biological relevance, cost savings, increased productivity and greater social acceptability. Here in the UK, surveys show solid public support for a move to non-animal methods (13,14). In other words, if the UK government were to support the non-animal testing market, not only would the potential for growth be greater, but the majority of Britons would likely endorse the move.

Wherever you are in the world, it’s becoming increasingly hard to find a good argument against a shift away from animal models, isn’t it?