What began during the mid-twentieth century as broad research focused on combining genetics and developmental biology has evolved into the field we currently refer to as epigenetics. The idea that environmental factors can trigger epigenetic changes reflected at different stages throughout a person’s life and even in later generations is controversial, as scientific convention states that genes contained in DNA are the only way to transmit biological information between generations. However, new scientific evidence demonstrates that our genes are modified by the environment all the time, through chemical tags that attach themselves to our DNA, switching genes on and off.
The number of treatments formulated each year has increased dramatically over the last 10 years due to technological advancements within the biomedical field. However, formulation and development does not necessarily equate to launch on the market, as many treatments are deemed ineffective, inferior to those already on the market, or unsafe.
Therefore, all treatments produced by pharmaceuticals must undergo rigorous testing before being launched on the market. It would of course be premature and dangerous to immediately commence the testing of a new treatment in human subjects. As such, scientists take to studying the effects in models, which can include cell lines and non-human animals. Whilst it has been debated time and again whether it is ethical to use animals for scientific research, this blog will focus on the scientific validity of using such models.
Millions of animals are used for experimentation and testing every year. These can include mice, rats, rabbits, pigs, sheep, and monkeys. Animals such as mice and rats are more frequently used as they are smaller and therefore easier and relatively cheaper to keep. The idea behind animal experimentation or vivisection is this: humans and many non-human animals share an evolutionary history and therefore, it should be possible to make some conclusions about human medical conditions using animals as models.
Indeed, there have been a number of seminal animal experiments that have changed the world as we know it and led to Nobel prizes. Some famous examples include Sir Alexander Fleming’s discovery of penicillin and its curative effects in mice and Alan Lloyd Hodgkin’s discovery of ion channel mechanisms involved in neuronal excitatory transmission in cats, frogs and squid. These are the success stories.
But what are some issues with the validity of testing treatments in animals?
Yes it is true that we share an evolutionary history with the animals that are used for preclinical testing however, we are very distantly related. We have different anatomies, physiologies and biochemistries and therefore we cannot assume that effects in animals will be noted in humans. For instance, it is very difficult to assess the toxicity of a treatment in animal models such as mice or rats (which as outlined above are the most commonly used), because it is clearly unreliable to compare blood level toxicity between a 70kg human and a 350g rat.
Furthermore, many treatments are successful in animal models, but discovered to be ineffective, inferior or unsafe once tested in human subjects. Despite the ever growing budget that pharma puts towards the discovery of new drugs for treatments, very few make it to human trials and even fewer pass these vigorous clinical trials. There have been a number of instances when drugs, which showed great preclinical promise, ended up causing severe side effects and in some cases death in human clinical trials. Some reports have suggested that up to 90% of treatments that have passed preclinical trials fail at later stages. There has been a 100% failure rate in experimental vaccines against AIDS, despite these vaccines showing effectiveness in monkeys and chimpanzees.
There are also instances where drugs that were deemed as unsafe in animals have had tremendous effects in humans, which can result in misleading research. Aspirin for instance is toxic and ineffective when administered to most animal models, despite having great success in the amelioration of pain in humans. Given the poor success rate of many animal studies it is not hard to see that vivisection is not the most cost effective approach to assess efficacy and safety, as plenty of animal lives are wasted.
So, if animal models perform so poorly, what are the alternatives? With the ability to culture human cells in petri dishes, some scientists have suggested that cell cultures are more robust models as they offer more insight into human conditions than animal experimentation does and this method is often less expensive. It is possible to virtually reconstruct human molecular structures through computer models, which could be used more reliably than mice to text treatment toxicity for instance. Still these are artificial systems and results need to be assessed with caution.
Animal experimentation has resulted in major biomedical breakthroughs. However, there are some major limitations to using animal models and the results of these preclinical trials do not often correlate with the results from human trials. Minor species-specific biology can have significant effects on the validity of a drug in human treatment. As with any research using artificial systems, the data needs to be assessed cautiously.