Future of computer modelling in animal ethics

Computer simulations reducing animal use and improving accuracy of drug safety testing

11 August 2023

Computer models being developed by the Institute’s scientists will allow drug companies to predict the cardiac safety of new drugs more accurately and more ethically than testing on animals.

The simulations can be used to assess the safety of a whole range of drugs – ranging from antihistamines to antibiotics.

According to Dr Stewart Heitmann, who is leading the project alongside Dr Adam Hill, it’s a significant step forward in the Institute’s mission to achieve the three Rs – to Replace, Reduce and Refine the use of animals in research.

Dr Stewart Heitmann

Dr Heitmann says: “International guidelines dictate that every new drug must be screened for cardiac safety prior to conducting human trials. Historically, those tests were often conducted in animals like rabbits and guinea pigs – amongst other systems - to assess whether the drug inadvertently caused potentially fatal heart rhythm disturbances.

“It is increasingly recognised that computer modelling can not only reduce animal testing, it can also be more accurate in predicting whether a drug will cause cardiac side effects or not.”

Another benefit of computer simulation is that it can accurately classify drugs that have been deemed unsafe in the past, but don’t in fact cause arrhythmia.

Until recently, scientists focused on one specific ion channel – called the hERG channel - to ascertain if a drug is prone to induce abnormal heartbeats. If the drug blocked the hERG channel, then it was deemed unsafe.

Researchers have since discovered that the safety of a drug depends on multiple ion channels.

Dr Heitmann adds: “It’s more complex than we first realised. We can now see that multiple channels might be blocked, including the hERG channel, and that the effects can counterbalance one another. This essentially means that drugs can still be safe despite failing the hERG test, which is currently the gold standard.

“Computer modelling is proving incredibly sophisticated and accurate at assessing drugs for arrhythmogenic risk. In fact, our computer modelling approach can predict arrhythmias with around 90% accuracy, compared to 75% for the animal-based tests."

The flow-on effect is that the drugs deemed unsafe can now be re-tested through the new complex computer modelling.

Dr Heitmann says: “Pharmaceutical companies are obviously interested in recovering drugs that may have been prematurely rejected as unsafe. Such drugs could be brought back to market. For patients, this could mean a whole new range of beneficial drugs for a whole range of conditions.

“We can’t replace all animal testing in heart research yet, but this is a big step forward in reducing their use. It promises more accurate and cheaper safety testing, so it’s a win for both pharmacology and animal ethics.”

Dr Heitmann was recently awarded a grant from the Baxter Charitable Foundation to improve the cardiac safety of drugs without testing on animals. He has also been the recipient of a Medical Advances Without Animals (MAWA) Research Grant for the same work.

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