Podcast: Heart failure and vacuum field fluctuations

Host: Benjamin Thompson

Welcome back to the Nature Podcast. This week, we’ll be finding out about a new mouse model of heart failure.

Host: Charlotte Stoddart

And learning about energy fluctuations in empty space. I’m Charlotte Stoddart.

Host: Benjamin Thompson

And I’m Benjamin Thompson.

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Interviewer: Benjamin Thompson

First up on today’s show, I’ve been looking into some new research about heart failure – a very serious condition which is characterised by a weakness of the heart which can’t pump blood effectively around the body. It’s a debilitating, long-term condition which is most common in older people. There are a few different types of heart failure and of the most common is called ‘heart failure with reduced ejection fraction.’

Interviewee: Joseph Hill

That’s the kind of heart failure you get if you have a heart attack, for example, where the heart muscle is injured, part of it is dead and no longer able to contract, and the ability of the heart to expel blood is decreased. That is a disorder that is very common. We see it all the time and we have many, many, many tools to treat that.

Interviewer: Benjamin Thompson

This is cardiologist Joseph Hill from the University of Texas Southwestern Medical Center in the US.

Interviewee: Joseph Hill

Another type is heart failure with preserved ejection fraction (HFpEF). That is a disorder that is just as common as heart failure with reduced ejection fraction, in fact, nowadays, it’s more common.

Interviewer: Benjamin Thompson

Rather than failing to properly expel blood, HFpEF hearts have impaired ability to fill with it. Although these two types of heart failure have similar symptoms – for example, shortness of breath, exhaustion, swollen limbs – when it comes to HFpEF, the treatment options are very different.

Interviewee: Joseph Hill

We have nothing to treat this disorder and it’s a very frustrating clinical situation. What we typically do is we will diurese the patient to eliminate the excess fluid in their lungs and in their belly and in their legs, and that will make them feel better. We will treat their comorbidities, we will treat their hypertension, we will treat their diabetes, but we have nothing at all to treat the root of the problem, what is wrong with the heart itself.

Interviewer: Benjamin Thompson

One of the reasons for the lack of treatment options has been the lack of a suitable model to test them on. While animal models of HFpEF do exist, they don’t necessarily reflect all of the symptoms seen in humans. Joseph is hoping to change that and has this week published a paper in Nature detailing a new mouse model of HFpEF that he thinks mirrors the human syndrome more closely.

Interviewee: Joseph Hill

We took a very simplistic approach – that is, most patients with HFpEF are obese with diabetes and they have high blood pressure, so we decided to make a mouse that’s obese with diabetes and that has high blood pressure.

Interviewer: Benjamin Thompson

By feeding the mice a high-fat diet and administering a drug to raise their blood pressure, the team were able to mimic many of the characteristics of HFpEF in humans, including impaired filling of the heart, exercise intolerance and lung congestion. Having this model allowed Joseph and his colleagues to look for a mechanism underlying HFpEF in these mice. It turns out that an enzyme called iNOS was being overproduced in the mouse hearts. This enzyme makes the molecule nitric oxide, or NO, which is important for many physiological processes, so having increased levels of the iNOS enzyme was having effects on other proteins in the mouse hearts.

Interviewee: Joseph Hill

The animal is flooded with NO and what that NO does is it covalently couples to many, many, many different proteins, including one of them that plays a significant role in the unfolded protein response.

Interviewer: Benjamin Thompson

The unfolded protein response is a set of emergency measures that stressed cells activate when faced with a build-up of incorrectly folded proteins – something that is very bad for cells. In a number of heart disorders, the unfolded protein response is switched on in response to cellular stress, but in the HFpEF mice, it was switched off as a result of the excess nitric oxide. This was a surprise for Joseph, and could represent a new mechanism underlying HFpEF. The unfolded protein response was also found to be downregulated in heart biopsies from humans with HFpEF, showing some similarity between the animal model and the human syndrome. Joseph says though that this work is only looking at one potential mechanism, and there could be a lot more going on.

Interviewee: Joseph Hill

There are many proteins that are covalently altered by this surfeit of NO and we haven’t begun to look at all of them – there are many of them. So, what we have found is that this excess NO is crippling the unfolded protein response, but it’s entirely possible that there are many other events going on as well, that the NO coupling to other proteins is doing important things that we haven’t begun to figure out yet.

Interviewer: Benjamin Thompson

Regardless, just having an animal model of HFpEF that shows many of the symptoms seen in humans will likely be of benefit to other researchers, according to Elizabeth Murphy from the National Heart, Lung and Blood Institute in the US, who wasn’t involved in the study.

Interviewee: Elizabeth Murphy

The main utility of this to me as a cardiac researcher is it now gives a new tool to study drugs. HFpEF is 50% and growing of the patients with heart failure, and if I want to say does this drug work for HFpEF patients, I have no model to test it in. So, now I at least have a model and I think many researchers in the field will be testing their drugs on this model.

Interviewer: Benjamin Thompson

Elizabeth thinks that because HFpEF is caused by such a complex range of factors, care must be taken to tweak the new mouse model – perhaps by using different methods to induce the condition – to see if the downstream manifestations of HFpEF is the same each time. In humans, HFpEF affects more women than men, perhaps by as much as two to one. Elizabeth also says that this is something that needs to be considered when developing future models for HFpEF.

Interviewee: Elizabeth Murphy

The study seems to be primarily carried out in male animals, and I think it would be important to see whether if they did these studies in female animals, would they get a similar result? And furthermore, they show a role for iNOS in the unfolded protein response. Since there are metabolic differences particularly in the way iNOS is regulated in males and females, would they get a similar upregulation of iNOS in female mice?

Interviewer: Benjamin Thompson

Joseph told me he is currently researching how sex differences in mice might affect HFpEF. He also says that the current animal model is just a start and won’t necessarily be representative of everyone with the condition.

Interviewee: Joseph Hill

HFpEF is notoriously heterogeneous and I don’t mean to suggest that this model is HFpEF for everybody. I believe, based on my reading of the literature, that this is sort of garden-variety HFpEF – it is certainly a very common manifestation – but I don’t mean to suggest that this is all of HFpEF because it’s probably not.

Interviewer: Benjamin Thompson

Whether this new model represents all of HFpEF or not, it gives researchers a new place to start when looking at the mechanisms underlying this complex and currently untreatable condition that affects millions of people worldwide. You can read Joseph’s paper, and a News and Views article about the work over at nature.com

Host: Charlotte Stoddart

Later in the show, we’ll be hearing about a new species of human that’s been discovered – that’s coming up in the News Chat. Up next though, it’s time for the Research Highlights, this week read by Nick Howe.

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Nick Howe

Bilbies are a type of marsupial with rabbit-like ears, pointy noses and long tails. Other than being adorable, they are also master engineers, capable of digging complex burrows in a matter of hours. By mounting cameras near bilbies’ burrows across north-western Australia, scientists from Murdoch University observed a plethora of other animals enjoying the bilbies’ hard work. At least 45 species, including lizards, birds and mammals, were observed hanging out around the bilbies’ burrows. The scientists suggest that the burrows provide shelter from the harsh, arid environment. After a wildfire, certain species such as mice and small reptiles were more likely to seek out the shelter of the burrow. Dig up that research over at the Journal of Zoology.

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Nick Howe

Back to the Future Part II promised us that flying cars would be available by 2015. Now, it’s 2019 and we’re still without our aerial autos. But this hasn’t stopped scientists from the University of Michigan calculating whether having flying cars would be a viable option for sustainable transport. The authors modelled the greenhouse gas emissions of flying cars based on existing and theoretical designs and compared these to petrol-powered and electric cars. They found that for short trips, these soaring sedans would likely produce more emissions than other vehicles. For longer trips with more passengers they could be slightly more sustainable compared to other cars as they fly directly from point to point. But for the time being, despite the proclamations of Doc Brown, where we’re going we still need roads. Fly over to that research in Nature Communications.

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Host: Charlotte Stoddart

Next up, we’re talking about quantum physics and something that relates to Heisenberg’s uncertainty principle. This principle dictates that the more accurately we measure a particle’s location, the less sure we’ll be about how fast it’s moving. A similar relationship applies to energy and time, so that in a narrow enough window of time, the energy within a particular space is uncertain. The result of this is that empty space is not actually empty. Instead, even in a vacuum we get fluctuations in the electromagnetic field, as pairs of particles and antiparticles flit into and then out of existence in the briefest of moments. Such fluctuations were first observed directly back in 2015. But now, a team from Zurich think they have measured the characteristics of those fluctuations for the first time. Our reporter, Lizzie Gibney, caught up with one of the authors of the new paper, Ileana-Cristina Benea-Chelmus, and she started by asking if these fluctuations are so brief, why do we care about them?

Interviewee: Ileana-Cristina Benea-Chelmus

We care about them because they have actually implications in our everyday life, and one very striking example of this is the fact that these vacuum fluctuations are the reason for which we can see atoms or collections of atoms emit light, and one very, let’s say, hands-on example for this is light-emitting diodes. They emit light and we are using them every day but without vacuum field fluctuations they would not emit any light.

Interviewer: Lizzie Gibney

Can you just flesh out a bit how it is that light-emitting diodes rely on these fluctuations?

Interviewee: Ileana-Cristina Benea-Chelmus

So basically, light-emitting diodes rely on so-called ‘spontaneous emission’ in which an atom which is excited has extra energy and transforms its energy into light, and this process can only occur if vacuum field fluctuations are present at the very location where the atom is located as well.

Interviewer: Lizzie Gibney

So, they sound pretty important but also like they might be very, very difficult to measure if they’re so tiny and also occur so fleetingly. How do you go about measuring something that’s almost nothing?

Interviewee: Ileana-Cristina Benea-Chelmus

First of all, you have to make sure, of course, that what you are measuring is not something else besides these very tiny fluctuations that occur in time and space. And what is important to know about this is that these vacuum field fluctuations happen also in a space which is completely devoid of matter, a so-called vacuum. So, if you want to measure only them, you have to realise measurement conditions on apparatus which simulates this void, so this is one aspect of it. The other aspect is how do you go about to really detect these fluctuations? But what it is important to know is that the fluctuations that we measure in this experiment are fluctuations of an electromagnetic field, so we measure an electromagnetic wave and the electric field that is contained in this electromagnetic wave. In some sense, it is equivalent to measuring a voltage.

Interviewer: Lizzie Gibney

So, how did you go about doing it in this case? What was your setup?

Interviewee: Ileana-Cristina Benea-Chelmus

We realised this pure emptiness by creating a measurement apparatus which we cooled down close to absolute zero temperature and which we put in absolute darkness, such that no light can go in from the outside and in such a way that we removed all matter and all particles of light that are inside and then we placed into this environment a special type of crystal which changes its properties upon an applied electric field, and as such it will also change its properties when vacuum field fluctuations – which are fluctuations of an electromagnetic field – travel through this crystal and by measuring the characteristics of these crystals, we measure the vacuum field fluctuations.

Interviewer: Lizzie Gibney

And what were you able to reveal about the vacuum fluctuations in your experiments?

Interviewee: Ileana-Cristina Benea-Chelmus

What we were particularly interested in in this experiment was to see how vacuum field fluctuations in a certain location in space and at a certain point in time are similar or antisimiliar or completely independent from vacuum field fluctuations happening at another point in space at another moment in time, to see how correlated they are across time and space. And we can go to the very root of the characteristics of these vacuum field fluctuations and determine the frequency with which the electric field is oscillating. So, we really proved the wave nature of these vacuum field fluctuations.

Interviewer: Lizzie Gibney

And did it match with what you would expect from what quantum physics tells us?

Interviewee: Ileana-Cristina Benea-Chelmus

Our experiments agreed very well with existing quantum theory, both in behaviour as well as in amplitude, and this is quite remarkable because it tells us that the world in which we live, at least in this very example, is very well described by the quantum theory that has already been established a long time ago, and we were able to prove this in our experiment.

Interviewer: Lizzie Gibney

And being able to describe the amplitude and the frequency of these vacuum fluctuations, how might that help us with future experiments or understanding other phenomena?

Interviewee: Ileana-Cristina Benea-Chelmus

In the future, we hope that the technology that we have developed will be useful also in other types of experiments to enhance the accuracy of existing experiments and also to make other quantum phenomena accessible experiments.

Interviewer: Lizzie Gibney

Do you think that when Heisenberg came up with his uncertainty principle, he had any idea that someday somebody would actually be able to measure the fluctuations that it entailed?

Interviewee: Ileana-Cristina Benea-Chelmus

I think as a physicist you always have this hope that this will happen one day and honestly, I think it’s just a matter of technology. It is not our task as physicists to explain why the world is as it is, but what we can do is we can try to come up with models which describe it in the best possible fashion. And then on the other hand, to have these very important experimental demonstrations which show us that we are on the right path, even though we might not have understood everything so far, we are continuing our work into unlocking the mysteries of nature.

Host: Charlotte Stoddart

That was Ileana-Cristina Benea-Chelmus, who is now at Harvard University, and she was talking to Lizzie Gibney. You can find the paper they discussed along with a News and Views article over at nature.com.

Interviewer: Benjamin Thompson

Finally then on this week’s show, it’s time for the News Chat, and I’m joined here in the studio by Matthew Warren, one of the reporters here at Nature. Matthew, thanks for stopping by.

Interviewee: Matthew Warren

Yeah, it’s always nice to be here.

Interviewer: Benjamin Thompson

Our first story today revolves around an archaeological find. What’s been uncovered?

Interviewee: Matthew Warren

Well, scientists have found a handful of bones and a few teeth as well in this cave on an island in the Philippines, and they say that based on what these bones and teeth look like, these belong to a previously unknown species of human.

Interviewer: Benjamin Thompson

I mean it’s notoriously difficult to find complete skeletons of ancient hominins and it sounds like that’s the case here as well.

Interviewee: Matthew Warren

That’s right. There’s just two feet bones, two hand bones, a single thigh bone and seven teeth – that’s the only remains that have been found.

Interviewer: Benjamin Thompson

And this has been enough then to suggest that this might be a new species?

Interviewee: Matthew Warren

Yeah, so the scientists compared the kind of morphology – so how these bones and teeth looked like with other species of human – and they found that there are enough differences to make them believe that it belonged to a species which hasn’t been described before.

Interviewer: Benjamin Thompson

And what’s this species called and what do we know about it?

Interviewee: Matthew Warren

Well, the island that the bones were found on is called Luzon, and so they’ve name the species Homo luzonensis. In terms of what we know about it – actually fairly little. They’ve described what these bones and teeth look like and they’re quite a lot smaller than those of most other hominin species, so they think that this species would have been quite small, similar to another species which was found in 2004 on another island, the island of Flores in Indonesia.

Interviewer: Benjamin Thompson

And yes, that was called the ‘Hobbit’ I believe.

Interviewee: Matthew Warren

Yeah that’s right, the ‘Hobbit’, or if you want to give it the correct scientific term, Homo floresiensis.

Interviewer: Benjamin Thompson

Well, thinking about this new species then, so Homo luzonensis, do the bones give any clue as to what life was like for this diminutive hominin and do we have any idea how long ago it lived?

Interviewee: Matthew Warren

Well, the bones do provide some clues as to what these early hominins might have done. In particular, there are curved toe bones which suggest that climbing might have been really important for them. The bones have been dated to about 67,000 years ago, so that’s probably around the time when the species was on this island and at the same time obviously, you had Homo sapiens, you had Neanderthals, you had Denisovans, all these other species that were in parts of Europe and Asia.

Interviewer: Benjamin Thompson

Well, I mean you mention a bunch of other species there – do we have any idea how this new species fits on to the family tree?

Interviewee: Matthew Warren

One of the problems when you discover these bones in warm areas like the Philippines is that the DNA is usually degraded and so in this case, the researchers haven’t been able to extract any DNA from the remains. That means they’re not able to place it in our family tree.

Interviewer: Benjamin Thompson

Well, what happens next? How are researchers going to find out more about Homo luzonensis and how quickly will they be able to confirm that it is indeed a new species, for example?

Interviewee: Matthew Warren

I’m not sure how quickly that argument is ever going to get resolved. One of the things that could potentially be useful is protein analysis, so whereas DNA gets degraded pretty quickly, sometimes proteins can last for longer and it could potentially be possible to extract proteins from these remains and analyse them to get some idea of who they are and how they relate to other hominins.

Interviewer: Benjamin Thompson

Well, let’s move on to our second story today Matthew, and it couldn’t really be more different from the first if we tried. This one is about impact factors and how maybe they’re relating to academics’ promotion chances. Maybe before we start there you can explain to our listeners who don’t work in academia what an impact factor is.

Interviewee: Matthew Warren

Well, an impact factor is a metric that journals use to keep track of the number of citations that the articles that they’ve published have received in the previous two years.

Interviewer: Benjamin Thompson

And this is a number that’s used kind of as a league table, as a ranking system?

Interviewee: Matthew Warren

Yeah, that’s right. So, publishers often promote the number in a way to kind of reflect the quality of their journal. But impact factors have been tied up into other aspects of academic life, and so sometimes, for example, universities use them to kind of judge scientists in terms of deciding when to give them pay raises or move them into tenure.

Interviewer: Benjamin Thompson

And presumably this is something that academics aren’t necessarily delighted about?

Interviewee: Matthew Warren

Yeah, and there’s been a push to kind of move away from using these kinds of metrics in performance reviews.

Interviewer: Benjamin Thompson

And is that happening?

Interviewee: Matthew Warren

Yeah, so according to a new paper published this week in PeerJ Preprints, it doesn’t seem to be the case. So, a team of researchers gathered over 800 documents that relate to the promotion and tenure process from over 100 different universities in the United States and Canada, and they looked at whether or not they mentioned impact factor in those documents. And a large chunk of those documents did indeed mention impact factors, which suggests that those kinds of metrics might be being considered when universities decide who to promote.

Interviewer: Benjamin Thompson

And does the paper break down things by institution – are some using impact factors more than others, for example?

Interviewee: Matthew Warren

Yeah, they split the universities up into those that grant doctoral degrees and have a really strong research focus, those that grant master’s degrees and those that mainly focus on bachelor degrees, and they found that it was those research-intensive, doctoral-degree granting universities that were the worst, so 40% of those universities mentioned impact factors in those documents.

Interviewer: Benjamin Thompson

What are researchers saying about this finding then?

Interviewee: Matthew Warren

Well, we talked to one researcher, Elizabeth Gadd, who’s a research-policy manager at Loughborough University here in the UK, and she said that “it suggests that those organisations may not have properly thought through what they are looking for in their faculty.”

Interviewer: Benjamin Thompson

And so maybe what can be done instead then? I guess a league table is a shortcut but is there a better way? What could it be?

Interviewee: Matthew Warren

Well, we also talked to Stephen Curry who’s a structural biologist at Imperial College in London, and he says that “researchers deserve to be judged on the basis of what they have done, not simply what they have published.”

Interviewer: Benjamin Thompson

Well, thank you for joining me Matthew. Listeners, to read more about these stories, head over to nature.com/news. Speaking of news, there has been a late breaking story today about black holes. Now, this didn’t happen quite in time for the show, but check @NatureNews on Twitter for the latest developments, and listen out for a special News Chat extra coming later on this week.

Host: Charlotte Stoddart

And that’s it for this week’s show. If you’re interested in the new species of human and you’d like to see some of the bones and teeth that were mentioned in the News Chat, I’ve made a video about it and you can find that at youtube.com/NatureVideoChannel. I’m Charlotte Stoddart.

Host: Benjamin Thompson

And I’m Benjamin Thompson. See you all next time.