What is the heart of the research?

The British Heart Foundation's former Medical Director Peter Weissberg talks about the biggest changes he's witnessed in his career and where the next big developments in cardiovascular research might come from.

What have been some of the biggest changes you’ve witnessed?

When I was a junior doctor, somebody would come in with a heart attack and all we could do was give them a painkiller, put them in a bed and watch them either recover or die. Now, we understand how a heart attack occurs, which is through a blood clot forming spontaneously inside somebody’s coronary artery.

That’s largely thanks to BHF-funded research by Professor Michael Davies. That opened the door for drug companies to start making thrombolytic [clot-busting] drugs. We funded an Oxford-based trial that showed that if you treated patients with aspirin and a clot-busting drug, you could reduce heart attack-related deaths by 42 per cent. Moving on from that research led by BHF Professor Ball in Leeds showed that if you put them on an ACE Inhibitor after a heart attack, their chances of survival were higher still. 

What are some of the remaining challenges?

The number of people surviving a heart attack, or two or three heart attacks has increased but as a result of surviving those heart attacks they now have very badly damaged hearts. They are living with heart failure, which is miserable. There are drugs, which we’ve helped trial, which help improve the outcome for people with heart failure but it’s still a very devastating condition. We are funding science now in the laboratory to try to understand how to repair a damaged heart in the hope that in the next few years, there will be new treatments for people with badly damaged hearts that could reduce their heart failure.

How do we decide where best to spend our research budget?

The real answer to that is you don’t know what could benefit somebody in twenty years’ time, and you don’t necessarily know where the science is going to go either. But what you always need is good scientists who you can trust to do an experiment and learn from that experiment whether it goes the way they expected it to or not. It’s rare that you don’t learn anything in science. We spend a lot of money on developing scientific careers. 

It’s rare that you don’t learn anything in science.

Professor Peter Weissberg

What are some of the promising fields?

Genetics is a very promising area of science. We can do genetic tests and again a lot of that has come out of British Heart Foundation funded research. Familial Hypercholesterolemia and Hypertrophic cardiomyopathy are two potentially fatal conditions dictated by single gene defects and our research has shown what the gene defects are and how to test patients for those defects. 

In the case of FH, we know how to treat it with statins, which is a great success story. So, patients with a genetic defect that puts them at risk of premature death can be identified and successfully treated. The next phase is to understand how the tiny variations we all have in our genes combine to make us susceptible to, or protected from, a particular disease, and that means we have got to integrate an enormous amount of genetic information.

How are we going to analyse all those data?

The next big phase of genetics will be informatics, bringing together masses of data and trying to understand how hundreds of small genetic differences combine to put people at risk of a particular disease. That doesn’t necessarily mean that they will get it. It just means they are more at risk than somebody who doesn't have that combination of genes and we have to determine how we are going to use that information.

We’re starting to put money into big data not just from tens but from thousands or even hundreds of thousands of people. Those data may include patients' behaviours, for example, whether they smoke or not, and their treatments as well as whole DNA sequences or sequences of particular genes. There are huge amounts of data that needs very sophisticated computing and a lot of informatics expertise to decipher what the messages are in all those big pieces of information.

What exciting developments are being worked on in the lab?

One interesting area is inducible pluripotent stem (iPSCs) cells. At the moment if somebody has a genetically determined heart condition that could kill them, we can’t study their heart because it is inside them. What we need to be able to do is to study their heart cells and understand how they misbehave and then try different ways of modifying that behaviour.

With iPSC technology you can take a slither of skin from people who have got this condition because all of your cells, even your skin cells, contain your entire DNA. You can change those cells in the laboratory into stem cells, and then change those stem cells into heart cells so in effect what you end up with is the patient's own heart cells in a dish.

That means you can test their heart cells to find out what the fundamental problems are, and try different drugs and different strategies to see if you can come up with something that modifies the way the heart cells work in a culture dish. Then hopefully you can move on to try to treat those people in the future with a drug that’s almost specifically designed for their own heart cells, and their own heart problem.

It sounds complicated, how long will all this take?

Recently, we’ve launched a translational research award. What we mean by that is that traditionally the BHF has funded laboratory scientists in universities to look at molecular mechanisms. If scientists then came up with what looked like a promising new target for a drug or even a molecule that could be a drug itself then by and large we’ve expected the drug industry to then move in and pay for the  research that develops that through to a drug.

The problem with that is industry won’t pay for that research until it’s pretty certain that it’s going to produce an effective and safe drug.. So, it’s clear to us that we have to bridge that gap between exploratory work done in universities and the drug development research done by industry by funding research that provides the evidence that industry needs to have the confidence to put money into backing something as a new drug.

It's clear to us that we have to bridge that gap.

Professor Peter Weissberg
BHF Medical Director

We’re having to think about science that is aimed specifically at drug development for example by asking ‘if we modify this molecule in a particular way, can it become a molecule that the drug companies believe is likely to be safe and effective enough for them to invest in?

What technologies that are about to come to fruition?

Gene therapy has been talked about for around 15 or 20 years, and some would say has not fulfilled its promise.  But the laboratory science has now been done, and research we’re part funding at Imperial College is using gene therapy to treat patients with heart failure. 

Why problem statement is the heart of research?

Is sop the heart of research?

Why is research considered to be the heart and soul of writing?

What is known as the heart of the research process where the findings of the research can be found using tables and graphs to interpret the results of your research?