Animal tests are an essential, expensive and heavily regulated process that needs to be carried out if medical science is to keep moving forward. Bodies are complex, unpredictable structures, and while scientists may have a good idea of whether or not a new substance could be harmful in their preclinical tests when they develop it, you can never really know what will happen until it’s entered a body.
Of course, as well as determining whether or not new products are harmful, researchers also need to check if they’re actually going to work – that is, will they pass the slalom of filters and mechanisms our bodies have evolved to keep potentially harmful substances away?
And on top of scientific necessity is the giant web of international regulations that govern testing. “We need to comply with EEA (European Economic Area), EMA (European Medicines Agency) and FDA (Food and Drug Administration) requirements to get a new drug approved,” says Dr. Klaus-Dieter Bremm, Head of Animal Management at Bayer. “There are also additional requirements under German pharmaceutical laws, and international harmonized guidelines.”
Excitingly, however, several broad categories of technology and process are actively reducing the need for animal testing.
The technology potentially changing the future
Testing methods fall into three distinct types: in vivo, in vitro and in silico testing, and all are in a state of transformation.
- In Vivo: Coming from the Latin for in life, in vivo testing involves the testing of new products or processes within living organisms. This includes both animal testing and human clinical trials – but with new technology it is becoming a less invasive method than before.
- It’s even allowing scientists to move beyond the traditional confines of in vivo experiments. For example, advances in neuroimaging techniques are giving scientists more penetrating insight into the brain than ever before. Microdosing1 is allowing researchers to see how small quantities of chemicals behave in the body, without exposing human test subjects to the usual risks of a full clinical trial.
- In Vitro: Latin for ‘in glass’, in vitro testing refers to testing done in a controlled environment, outside of a living organism – think test tubes and petri dishes. In vitro testing has been around for a while, for example in the form of cell cultures, and new developments are enhancing its viability as an alternative to animal testing.
- For example, 3D bioprinting2 allows scientists to create and study isolated sections of human tissue, in all its biological complexity, without a living organism attached. This can extend to diseased tissue: “With 3D bioprinting, you can print tumor tissue, for instance, as it is in the human body. It’s the same cells in the same layers. And this may be of tremendous value in early phases of research” says Dr. Bremm. Bioprinting can also replicate complex sets of multiple types of tissue. “You see people also attempting to replicate the immune system in, for example, a 3D model of the liver.”
- In Silico: Latin for ‘in silicon’, in silico testing needs no living tissue at all. Instead, experiments are conducted in computer models that allow scientists to artificially simulate biological structures and processes.
- For instance, the Virtual Liver Network3 (an alliance of 69 research groups and 200 scientists collaborating across Germany) has worked over the last five years to create a computer model of how the liver metabolizes various substances. It can model the liver in various states, such as in someone with toxic liver damage, or fatty liver disease, both of which can affect the rate at which metabolism takes place. Technologies like this offer massive time-saving advantages – rather than trialing drugs one-by-one on test animals, simulations like those being developed by VLN, can process 100,000 compounds per hour.
Looking beyond the barriers
However, these alternative testing methods are still at an early stage and there is some way to go before they can be routinely used.
“Despite the importance of the topic only relatively few people are currently working on alternative testing methods. But the efforts we are undertaking to explore new technologies and methods which no longer rely on experimental studies on animals demonstrate our ambition in this field,” says Dr. Bremm.
Once the technical hurdles have been crossed, the next step would be convincing lawmakers of the reliability of alternative testing in terms of predicting effectiveness and safety. “I think if we move ahead with alternative methods, educating regulators will be very important because they have to buy into this concept,” says Dr. Bremm. “But we already sense their willingness to adopt new methods and to change the existing regulatory environment if they are provided with convincing data.”
Despite the challenges, scientists like Dr. Bremm see a bright future in these technologies – including their potential to eliminate animal trials altogether. “I hope one day we’ll no longer need animal testing. And my personal guess is, we might be able to see that rather sooner than later and probably even in less than 20 years.”
- Indian Journal of Pharmacology, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025138/
- CERST, IUF – Leibniz Research Institute for Environmental Medicine, http://www.iuf-duesseldorf.com/cerst.html
- Virtual Tests for New Therapies, Bayer Research Magazine, https://www.research.bayer.com/en/virtual-medicine.aspx