Simulating a human heart

Can we simulate parts of the human body, to speed up the development of new therapies and the discovery of new drugs? Katie Haylor heard how Oxford University’s Elisa Passini is doing this for the human heart... 

Elisa - What we do is to build computer model of the human heart, to understand more about how the heart works and what can be done to improve diagnosis and therapies for patients. We are very interested in what is called drug safety. So not really drug discovery, when people try to develop a drug that can treat a specific disease but after that, when they need to check that the drug is safe for the heart. And this applies to any drug, all drugs on the market need to be tested on the heart and we can do the test on our model.

Katie - I see, so before a drug goes into a human heart you want to make sure that it's safe and, of course, you can't do that by testing it on a human heart. You need to have a model.

Elisa  - Exactly. So what is done currently is animal testing and then if a drug results safe in animal testing it goes through clinical trials. But we would like to go even before these animal testing and use our computer models, which are human based, to try and predict, early on, what would be the effect on our patients.

Katie - You might have an early candidate, put it through your model and say “uh uh” this is not going any further?

Elisa - So they test, let's say, 10 candidates with our models, they see which is the best one and then they move forward, but instead of testing all 10 they make a selection before, based on our results, to reduce the animal experiments down the line. That's also one of our aims, we are really interested in contributing to a reduction of these experiments.

Katie - So tell me about these models, then, how on earth do you build something on a computer as complex as a human heart?

Elisa  - You need to do experiments to understand what's going on inside the cell: all the little processes, all the little particles moving and you write that as equations. So in the end our models are a sum of mathematical equations that represent the behaviour of a human's cardiac cell.

Katie - And what kinds of features of these cells or the bits in the cells do these equations model, are they how they're behaving? How they're moving? What what are you looking at?

Elisa - It’s more the electrical activity we're interested in and this is because the cardiac side effects when taking drugs is usually an arrhythmias, which is an irregular rhythm of the heart and is due to the electrical activity. So what we study is the ion that are moving in and out the cell through ion channels. So our equation model these ion channels and the little particles moving in and out that produce currents.

Katie - So these things like what, Potassium?

Elisa - Yeah, sodium, calcium. So we go from the subcellular level to the cellular level and then we can also put many cells together and get to a tissue or an organ level.

Katie - Wow! And all of that is being portrayed in terms of equations? That's a lot of equations!

Elisa  - Yes!

Katie - So now you've got this model, how good is it?

Elisa  - So I would say it’s really good! What we have done is some evaluation studies with drugs that are already known, because first we need to prove to pharma companies, for example, that these models work. So we took drugs that were on the market, or they were withdrawn from the market because they had side effects for the heart, we tested these drugs and we predicted the risk or safety with almost 90 percent accuracy.

Katie - Thing is, not all hearts are the same, maybe things like age might be a factor, so what kind of heart are you building? Is this a generic heart or are you factoring in variation?

Elisa - Until, I would say 2010, what was using computer models of cardiac cell, was mostly an average model. So we had one model of the heart that was sort of representing everyone. So the method we developed is a sort of random generation of cells based on the idea that we are all similar. So, of course, cardiac cell will have the same mechanisms inside. But, for example, I may have more potassium channels than another person or sodium channel or calcium channel and we can model these by assuming a sort of random variability of these ion channels in the membrane.

Katie - So looking ahead then, could this actually be used in future to make a very specific, individual model of a heart? For instance, if you're trying to diagnose a potential condition in someone?

Elisa - We would like to get there and we actually started some works in this respect. What we do is we collaborate with hospitals and from them we can get images from patients and data about, for example, a genetic mutation or a specific disease. From the images of the patient we can get the geometry of the heart of these patients and then we can incorporate our models into patient specific geometry. And, for example, if someone had a heart attack or has a scar in the heart as a result of this heart attack, then we can include the scar and see what a drug would do to improve this heart conditions or what drug wouldn’t be safe because of this scar, for example.

Katie - How much precedent is there for computer modelling different parts of the body? Have other people done it for kidneys, liver, lungs, other organs?

Elisa  - Yes, definitely there are models, for example, of bones and muscles. As for organs, I would say the heart is quite advanced, compared to the others, and this is because it’s been around for like 60 years. So there are people doing modelling of kidney, gastrointestinal system, neurons. So, yeah, there are lots of people working on computer models of human body and physiology. And the idea is in the near future, maybe, we'll get to a point of having a whole virtual human, all simulated.l simulated.