Transcript
RICHARD HOLLIMAN
Hi. My name is Richard Holliman and I’m one of the Block 1 authors on S350 Evaluating contemporary science.
I’m here today with Martin Bootman, who works in the School of Life, Health and Chemical Sciences at The Open University.
We are here to discuss how science progresses.
So Martin, what’s your current topic of enquiry?
MARTIN BOOTMAN
So, my principle interest is how the cells in the body communicate with each other.
In particular, I’m interested in hormonal communication. So, that’s the way in which cells use factors that they secrete and then travel to another cell, engage with that cell, and cause it to change its activity. That’s what we study.
In particular, we’re interested in what hormones regulate the activity of the heart; what makes it beat faster and contract in a stronger way to pump more blood. That’s our key interest.
RICHARD HOLLIMAN
Cool. That’s really interesting. So I’m kind of interested in what do you see as the key characteristics of being a successful scientist?
MARTIN BOOTMAN
Well, I think number one, you’ve really got to have an enquiring mind so, you’ve got to look at the world with a sense of wonder and fascination, and perhaps also question things a little bit as well.
So, when you hear information you don’t just absorb it, you actually process it a little bit, and I think that’s what all scientists do, certainly the ones that then go on to develop questions that they can test in a kind of laboratory or a research environment.
I think you’ve also got to be quite dogmatic, a little bit. You’ve got to have perseverance, because we take small steps in science.
We develop questions and we answer them quite slowly, because systems that we study are complex, and sometimes it’s difficult to interpret the data that we get, the results that we find.
Sometimes it’s difficult to think of a new way of researching something, so it can be quite slow and it requires an awful lot of perseverance.
RICHARD HOLLIMAN
Okay. So what would you say is currently agreed knowledge in your discipline area?
MARTIN BOOTMAN
Well I think there’s lots.
Work on the heart, for example, has been going on all the way back to Sidney Ringer, you know, back in the 1800s.
So, there’s a lot of basic physiology that’s known and universally accepted about how the heart works, and that’s been added to over the centuries, over the decades, and that’s well grounded.
We know what the heart does. We know the structure, the anatomy of the heart, and we know its basic physiology.
Where modern research comes in is actually understanding the nuances of what goes wrong.
So, although we understand the anatomy and the basic structure of the heart and its function, what we don’t understand is some of the disease situations, some of the things that make the heart perform badly. How do they occur?
And in particular some of the genetic mutations that are very subtle in their effect, but in the lifetime of the person where your heart has to beat for seventy years, and pump essentially like a tanker-and-a-half worth of blood around your body, one genetic mutation that might have a very low penetrance, that means it might not have a very obvious kind of effect, in your lifetime that could lead to heart failure.
But why? And why does it take a billion beats before that heart failure is evident? Why is it not more penetrant earlier on?
So, those kind of things have really waited for an explosion in the techniques we call molecular biology, which enable us to go back and actually either correct that mutation, or to force that mutation to happen in certain situations, and then we can look at the outcomes.
RICHARD HOLLIMAN
Okay. Could you tell us a little bit about your contribution to this kind of area?
MARTIN BOOTMAN
Yes, so my group for many years actually studied how cells use calcium as a messenger, and calcium inside cells is what we call a pleiotropic messenger – it does many different things.
In fact one of the first things that happens to everyone in life when a sperm meets an egg is a rise in the calcium concentration and that’s necessary for many things.
In particular, it stops other sperm engaging with the egg, but it also starts the developmental programme, and stops cells being dormant any more, causing them to divide and causing them to form an individual. So a calcium signal is the first thing to happen to all of us.
With regard to the heart, every time the heart beats, every time there’s an electrical signal that pervades the heart it causes a calcium rise inside each of the cells of the heart, and it’s that calcium signal that causes the cells to contract, and the millions of cells that contract simultaneously generates the force that pumps blood around the lungs and the body.
So, we’ve taken our knowledge that we had from studying calcium signalling in other tissues to studies of the heart, and so that’s been our major contribution; actually understanding the fine detail of the dynamics of calcium signalling in heart cells.
RICHARD HOLLIMAN
Okay. And can you tell us a little bit about how your work has contributed to a kind of paradigm shift?
MARTIN BOOTMAN
So yeah it’s – it’s been a very interesting development for us since we started working on heart cells which is over a decade ago now.
I had a visitor who was a medic who came to work in my lab from Finland. So I had to think of a project for him to do and I said to him, ‘Mika, do you want to have a look at these channels?’, that we were studying at the time.
They were called IP3 receptors and just see if they are expressed in the heart and maybe have an idea – formulate some ideas of what they might do.
I didn’t think that project would lead very far if I was honest. I thought it would be just a quick look and see and it would satisfy him for his year’s sabbatical.
But actually, it opened up a whole new paradigm for us. Mika did his studies very diligently, and we got a data set that proves that the IP3 receptors are expressed in – in contractile myocytes – the heart cells.
We put the whole story together and we sent it off to a journal called Cell, which is a top level journal, but we weren’t successful in publishing it, and in fact we faced an awful lot of hostility.
So in the end we published it in a journal called Current Biology (Lipp et al., 2000).
We did take the data to conferences. We talked to other cardiac researchers. And they regarded it with mild cynicism at the time I think.
And the reason is because they’d been studying heart cells for so long that they thought they understood them very well, and there wasn’t really room for us with our new calcium channels to do anything.
They thought they really knew the system well, and we were interlopers, and they didn’t really appreciate our data at the beginning.
RICHARD HOLLIMAN
So in a way I guess you’re challenging their foundational knowledge and have come up against –
MARTIN BOOTMAN
Absolutely.
RICHARD HOLLIMAN
Those kind of challenges in a very kind of obvious way –
MARTIN BOOTMAN
Absolutely, and I think that’s why you’ve got to make sure that you’re thinking about experiments in a holistic way.
That you’re not simply going with how you think a system works, that you do have that capacity to think differently, to accept new data, to understand you might have very good experimental techniques to study what you’re interested in.
There’s still capacity for paradigm shifting new evidence to come along, and then you have to adjust, you have to incorporate that.
And actually in later years, you know, I’m pleased to say other labs demonstrated what we demonstrated, and we were actually proven through repetition, which is really the way that science becomes established as fact, as it were.
The most important thing of course is not – is not about personal satisfaction. It’s about the fact that we helped develop a new idea for something that might be a therapy for people who end up with heart failure, and that’s the point.
So, these IP3 receptors, expressed in the heart cells, do have a capacity to cause a slight elevation in the calcium levels over many, many heartbeats that can cause the expression of certain genes inside cardio myocytes, which are not good, and so we know now that IP3 receptors, if they’re activated in heart cells, can lead to a condition called decompensated heart failure.
I’m very glad that our contribution was acknowledged. It took us a while. It took us a while to convince people but, you know, what we’d managed to do is establish a new paradigm, which hopefully will have a benefit for health.
RICHARD HOLLIMAN
That’s excellent. Thanks very much.
MARTIN BOOTMAN
You’re welcome.