Podcast: Modelling early embryos, and male-dominated conferences

Host: Shamini Bundell

Welcome back to the Nature Podcast. This week, modelling early embryos…

Host: Benjamin Thompson

And the prevalence of male-dominated conferences. I’m Benjamin Thompson.

Host: Shamini Bundell

And I’m Shamini Bundell.

[Jingle]

Host: Benjamin Thompson

First up, reporter Nick Howe has been looking into the development of embryos.

Interviewer: Nick Howe

Scientists have got a pretty good idea of what goes on during the nine months of pregnancy, but for the very early stages, like when the embryo implants into the wall of the uterus – the so-called peri-implantation stage – not much is known.

Interviewee: Amander Clark

Implantation of human embryos into the lining of the uterus is a really mysterious process. It’s very difficult to study and this just happens to be the time in embryonic development where the cell types that will ultimately become the adult cells in a body will start to specialise and differentiate, and we know very little about that process in humans.

Interviewer: Nick Howe

This is Amander Clark, a stem-cell biologist who researches early human development. To better understand this mysterious stage, scientists use two main strategies. One is to use early-stage human embryos that have come from in vitro fertilisation clinics and have been consented for use in research. But these samples are rare, and due to current ethical guidelines, these embryos cannot be grown in the lab for longer than 14 days. The second strategy is to use stem cells, specifically pluripotent stem cells, which can change or differentiate into any cell type. These can be induced to form structures like those seen in a human embryo. The trouble with this is that stem cell cultures don’t fully mimic embryo development as the cells don’t organise themselves in the same way. So, how can researchers better understand the implantation period? Well Jianping Fu, a mechanical engineer, has been looking at how mechanical and chemical signals interact with stem cells. Through these manipulations of stem cells, he found something unexpected which may help.

Interviewee: Jianping Fu

So, somehow, to our great surprise, we observed that under some engineered, three-dimensional culture environment with suitable mechanical signals, human pluripotent stem cells self-organise. Somehow in the subset of those colonies, we start to observe some very interesting asymmetrical structures and these asymmetric structures resemble the core of the peri-implantation human embryo. So, this really got us excited.

Interviewer: Nick Howe

Jianping has been working to make a system that reliably produces these embryo-like structures. This week in Nature, he presents a microfluidic system – a tiny device that precisely controls fluids and contains pores within which embryo-like structures can form.

Interviewee: Jianping Fu

Basically, this microfluidic system traps little balls of human pluripotent stem cells in such a way that you can apply chemicals to cells only on one side of the ball. The microfluidic delivery will allow control over the timing of the chemical signal. More or less, you can now control when and where the cells will be exposed to chemical signals that are important to drive them to continue to differentiate and develop.

Interviewer: Nick Howe

So, rather than producing a ball of disorganised cells, this system allows Jianping to induce the formation of organised cell structures that more closely represent a developing embryo. Specifically, it allows asymmetric development. When an embryo implants into the uterus, typically the top and bottom will differentiate differently, leading to distinctive structures. Jianping was able to replicate this in his system and do it reliably.

Interviewee: Jianping Fu

Now, using this microfluidic system and this is very controllable and reproducible and scalable, we can generate these embryo-like structures with very high efficiency – more than 95% almost.

Interviewer: Nick Howe

Amander, who you heard from earlier and who wasn’t associated with this work, thinks this system is going to provide an important tool to understand embryonic development.

Interviewee: Amander Clark

I’m very excited about the utility of this technology because it can help us to understand diseases in the reproductive population and in particular, a focus on early embryo loss which occurs with these early miscarriages, and early miscarriages can occur in a many instances of pregnancy and using these models, we can help to understand and perhaps prevent women from experiencing early embryonic loss and infertility.

Interviewer: Nick Howe

Another potential use of this technology is that it may allow researchers to use these artificial embryos to study development beyond the current 14-day limit. The cells used in this research could not go on to become humans, as they lacked some critical structures required to do so. So, the 14-day rule may not apply, meaning that these model embryos could be used to understand more about the obscure early stages of pregnancy. But, when there are such similarities between models and real embryos, it does raise ethical questions. Ethicists are divided on how the 14-day rule should be applied in these cases. I reached out to a bioethicist, Giulia Cavaliere from Lancaster University, and asked her if she thought the 14-day rule would apply to Jianping’s model.

Interviewee: Giulia Cavaliere

So, the short answer to this question is no, it wouldn’t apply to this model, but there is, in a sense, a gap in the regulations about whether these are human embryos or not and what features of these models would make them resemble human embryos enough that the rule would apply.

Interviewer: Nick Howe

For Giulia, the interesting question is whether or not these models could replace human embryos in research altogether, especially as Jianping’s study was able to create these structures from stem cells that hadn’t come from human embryos at all. Regardless of whether or not these cell models will allow researchers to look beyond 14 days, they will help them better understand the mysterious early implantation stage of embryonic development. For example, it could be used to model the effects of drugs on an early foetus. Here’s Jianping.

Interviewee: Jianping Fu

I think it’s important for me to emphasise that this research area can lead to a lot of good. Such research is very important on the path to a better understanding of birth defects and other problems that happen in very early pregnancy.

Host: Benjamin Thompson

That was Jianping Fu of the University of Michigan in the US. You also heard from Amander Clark of the University of California, Los Angeles, and Giulia Cavaliere of Lancaster University in the UK. You can find Jianping’s paper, along with a News and Views article written by Amander, over at nature.com.

Host: Shamini Bundell

At the end of the show, we’ll be finding out about turning back time on a person’s biological age – that’s in the News Chat. Now, though, it’s time for the Research Highlights, read this week by the newest member of the team, Dan Fox.

[Jingle]

Dan Fox

For the first time, an international team of scientists have found the fossil tracks of baby turtles making a break for the sea. Fossils of seaside tracks are hard to come by, as the ocean has a habit of washing the stones that preserve them away, but a bountiful beach in South Africa has a glut of these rare relics. At this well-conserved cove, the fossil flipper prints of the little loggerhead turtles were discovered, preserving the moment when they crawled from their eggs to the safety of the sea. The fossils are likely a few-hundred-thousand years old, and the researchers believe the tiny tracks will give insights into the region’s climate at the time, as the turtles have specific temperature requirements for laying their eggs. Track that study over in Quaternary Research.

[Jingle]

Dan Fox

The largest of Saturn’s moons – the aptly named Titan – may have had an explosive past, according to new research. The surface of Titan is riddled with methane lakes, but how the basins of these lakes formed has been a bit of a mystery. Now, using data from a flyby of the Cassini probe in 2017, researchers have found similarities between these lake basins and craters on Earth that are formed by magma explosions. The scientists suggest that a warm period during Titan’s history caused liquid nitrogen to vaporise and explode, forming the holes, which were later filled with methane. Find that dynamite research over at Nature Geoscience.

[Jingle]

Interviewer: Shamini Bundell

Next up, Nature reporter Holly Else has written a feature about gender representation in science. In particular, she’s been investigating the phenomenon of ‘manferences’ or rather a conference where most of the invited speakers are men. Holly joined me in the studio to tell me more and started by explaining how on Earth she went about quantifying a manference.

Interviewee: Holly Else

Yeah, well that’s a really good question because it’s quite difficult, as I have discovered over the last few months. What we ended up deciding to do was to pick a selection of fields and crowdsource the top conferences every year that scientists in those disciplines would be going to and just counted up the number of male and female speakers who had been invited to the conference.

Interviewer: Shamini Bundell

So, you were manually looking through all these lists, writing people down, sort of trying to assess their gender.

Interviewee: Holly Else

Yes, I didn’t do it alone, but it was quite a lot of work and there were time when the name might be ambiguous, so we would have to sort of google the name until we found the academic profile on that person’s university website where often there was a photo, so that enabled us to make a judgement. Obviously, it’s only a judgement – we don’t know for sure what gender these names actually were. So, there are some limitations with our data.

Interviewer: Shamini Bundell

It sounds like a lot of different fields and a lot of different conferences – what’s the results that you found?

Interviewee: Holly Else

Yeah, well, we were actually quite surprised because one of the first one’s that we did was chemistry, and we kind of plotted the change over time for all these ten different conferences, and it was absolutely crazy. It was swinging from like 100% male to 40% male, and there was just no clear trend whatsoever. But in the other disciplines, there was some semblance of a clear trend where you could see things improving in terms of the representation of women at the podium. We’ve seen improvements in four of the five disciplines that we looked at.

Interviewer: Shamini Bundell

You’ve seen improvements, but where are we right now? If 50/50 is some sort of an ideal, how is science, in terms of the fields you were looking at, actually doing right now?

Interviewee: Holly Else

Well, that’s where it gets really difficult because although people might strive for a 50/50 gender balance, there’s sort of a big debate around whether that’s appropriate given that some fields of science aren’t 50/50 overall. So, you might have the new entrants into the science pipeline at the moment, so PhDs and postdocs, might be 50/50, but actually when you’re looking at the senior people in the field – the professors, the people who are invited to give these talks – the gender diversity action hasn’t really filtered through into that generation yet and so you might only have 20 or 30% of women in those posts anyway, so at a conference, should you expect to see half of the people on the podium who have been invited as women, or should you expect to see 20-30%? And that’s very much an active debate within these communities and you will be able to read a bit more about that in the feature.

Interviewer: Shamini Bundell

So, if you only have a tiny proportion of women in a field for whatever historical reasons and you want to sort of balance out your conference numbers, what are actually the pros and cons of doing that?

Interviewee: Holly Else

Some conferences, their organising committees know that they don’t have a 50/50 gender ratio in those top-notch speakers that they want to invite to their conference, but they still strive to achieve that because they feel that’s important for the next generation of women who are attending the conference, perhaps for the first time or at the beginning of their career.

Interviewer: Shamini Bundell

And there’s a story in your feature that’s quite extreme where you were talking about a conference where it was 100% male, which is quite extreme, and some women who then took over the conference and said right, not anymore.

Interviewee: Holly Else

Yeah, it was a fantastic tale to hear, and they got 50/50 women and men speakers, but that was just one year and then actually the next year it slipped back down towards being a ‘manference’ with probably too many men on the podium. What struck me as really interesting when I was talking to a lot of these people is the counter argument often is oh, there aren’t enough women, but actually when you scratch the surface of that comment, you find out that there’s more than enough women out there. Some conferences may have four or five invited speaker slots every year, some less than that, some obviously a few more, but there’s hundreds of capable women out there. It’s just a case of actually finding them.

Interviewer: Shamini Bundell

But people don’t just want capable, people want the top people in the field, but there’s a bit of a feedback loop with who people perceive as the top people in the field.

Interviewee: Holly Else

And that’s the problem. Someone I spoke to told me that if they go to a conference and they see it’s just another ‘manel’ or ‘himposium’, which is another word I’ve learnt on this adventure, their first thought is well, did these people really think about who are the best speakers for the conference or did they just think of the people that they know, perhaps they went to grad school with 20 years ago or people they saw at another conference, so it’s the same talk and that’s not the point of a conference. The point of a conference is to be bringing new ideas to the table every time.

Interviewer: Shamini Bundell

So, let’s say someone is organising a conference and they do want to do something about this, how do they go about this and how easy is it?

Interviewee: Holly Else

So, there’s lots of resources online about this, but one thing that we did sort of hear as I was reporting this piece was that those top-notch women can be in demand. So, a key thing that people told me is that actually, you often need to invite far more women than men to get the same numbers of yesses.

Interviewer: Shamini Bundell

So, does what you found make you optimistic about all these increasing trend lines you’re seeing in the number of women at conferences?

Interviewee: Holly Else

Well, I’d like to be, but I spoke to a statistician who told me that actually, we can’t really draw any conclusions based on the data that we’ve collected because the samples are so small. So, although we might have some nice sort of trend lines, actually, what’s really going on out there, we don’t know. But I think it’s a really positive story that actually, people have been moaning about this and they can still moan because there’s still a problem, but actually, there has been some concerted effort to change things.

Interviewer: Shamini Bundell

Brilliant, thanks for coming in and telling us about it.

Interviewee: Holly Else

No worries, thanks for having me.

Interviewer: Shamini Bundell

That was reporter Holly Else. For more on manferences, head over to nature.com/news to find Holly’s feature.

Interviewer: Benjamin Thompson

Finally then on the show, it is of course time for the News Chat, and joining me this week is Nisha Gaind, Nature’s European Bureau Chief. Nisha, thanks for stopping by.

Interviewee: Nisha Gaind

Of course. Hi, Ben.

Interviewer: Benjamin Thompson

Well, first up this week, listeners, I’m sure you remember last week’s News Chat when we talked about India’s Chandrayaan-2 lunar mission which was due to send down a probe to the lunar surface just after we recorded the show. Nisha, for a bit of an update, things haven’t necessarily gone too well.

Interviewee: Nisha Gaind

So, unfortunately, things seem to have gone awry with one part of this mission and that’s the lunar lander. The lander was supposed to land on the surface a few days ago, but unfortunately the Indian Space Research Organisation who is behind the mission lost contact in these nail-biting last minutes of the descent.

Interviewer: Benjamin Thompson

Yeah, and this was always going to be a tricky stage, these kind of final moments before touchdown. What do we know happened?

Interviewee: Nisha Gaind

So, what we know is that this lander, which is called Vikram, started its fifteen-minute automated descent process, but in the last three minutes when it was about 2.1 kilometres from the surface, some kind of trouble struck and the Indian Space Research Organisation lost contact with the lander.

Interviewer: Benjamin Thompson

Well, very disappointing I’m sure for all involved, but it’s not necessarily all bad news for the mission?

Interviewee: Nisha Gaind

Yes, that’s right. So, there were two parts of this mission, an orbiter and a lander, and as far as we know, the orbiter part of this mission which carries eight instruments is functioning normally and it is in orbit around the Moon and it has also, using its cameras, spotted Vikram on the lunar surface. So, that is a little bit of good news on the lander side. And there are currently efforts underway to try and re-establish contact with the lander, but this whole episode demonstrates just how difficult it is for a nation to perform what they call a controlled landing or a soft landing on the lunar surface.

Interviewer: Benjamin Thompson

Well, everyone’s keeping their fingers crossed, I’m sure, for some signs of life from the lander. In the meantime, though, let’s move on to our second story, and well, it’s the first tentative hint that a person’s biological age might be able to be reversed, and I have to ask you, Nisha, what is someone’s biological age?

Interviewee: Nisha Gaind

That is a really good question. We are obviously very acquainted with our own chronological ages – that which is counted in years from our birth date – but scientists also operate with something called the epigenetic clock, and this is a kind of construction that tracks what they term biological age, and this is something that could lag behind or be older than a chronological age because bodies behave differently and some bodies might look and operate like ones that are older than they actually are in years.

Interviewer: Benjamin Thompson

And epigenetics, as I remember from university, is what alterations to someone’s DNA chemically, maybe methyl groups being added on, that sort of thing.

Interviewee: Nisha Gaind

Yeah, that’s right. So, the epigenome is this collection of marks that exist on a person’s DNA sequence. They don’t change the sequence as such but they are these tags that are chemical modifications, and it’s the pattern of these tags that researchers look at because they change and accumulate over the course of a life, and they can be used to kind of judge somebody’s biological age and how it compares to their chronological one.

Interviewer: Benjamin Thompson

And well, what’s going on this trial then to try and maybe reverse those processes?

Interviewee: Nisha Gaind

So, we have this very tantalising, but we should say very preliminary finding from a trial of some drugs that this epigenetic clock can be reversed. What we have seen is that drugs in nine healthy people appear to have rejuvenated these people’s epigenetic clocks.

Interviewer: Benjamin Thompson

Right, and did this have any tangible effects on their physical health?

Interviewee: Nisha Gaind

Health is obviously comprised of lots of different things, but what we can talk about are these very specific things that were observed in the trial, and that is immune function and also the function of something called the thymus gland, and in fact, that’s what the trial was originally focusing on. Researchers observed that when they were given these drugs, and the drugs were a growth hormone and two anti-diabetes drugs, they observed that the thymus gland, which is important for immune function, appeared to rejuvenate. So, that’s to say that new tissue appeared there, it looked like the thymus gland of younger people and the same happened to the blood cell counts of these nine people, and the researchers say that in effect, the trial participants shed 2.5 years off of their biological age.

Interviewer: Benjamin Thompson

Well, small trial as you say – there were only a few participants. What happens next and where might this lead?

Interviewee: Nisha Gaind

Exactly, a very small trial, and it’s also really important to underscore that it didn’t have a control arm, so this is a very, very preliminary trial. The next steps here are to take tests of these drugs forwards, and to do, of course, a much bigger trial that has a control arm and to see whether these effects persist in a greater diversity of people and to see how strong they are. But researchers say that they are cautiously optimistic that the effect was valid.

Interviewer: Benjamin Thompson

Well, lastly on today’s News Chat then, Nisha, we have a list of the winners of this year’s Breakthrough Prize, which is of course one of the most lucrative prizes in science and mathematics.

Interviewee: Nisha Gaind

Yes, that’s right. These are the Breakthrough Prizes which are each worth US$3-million and they were awarded last week, and one of the prizes went to the collaboration who took the first ever picture of a black hole – that’s the Event Horizon Telescope team.

Interviewer: Benjamin Thompson

Well, this is a story we covered a lot on the podcast when it happened, and it was an amazing image. Often with big projects like this, there are hundreds of team members but the prize sometimes goes to just one person. What’s going to happen here?

Interviewee: Nisha Gaind

This was a massive effort. Physics collaborations in particular are renowned for being huge and often go into the thousands of people. In this case, 347 members of the collaboration will receive this prize, but it reflects the fact that this was an immense, coordinated effort. It took eight telescopes around the world and these researchers effectively built a telescope the size of Earth in the way that they harnessed these instruments, and this was powerful enough to capture this absolutely incredible image of a black hole that is a real leap forward in the fundamental research of these massive objects that populate the Universe.

Interviewer: Benjamin Thompson

Well, they certainly seem like worthy winners in this instance, but it’s not just physicists who have received prizes this time round.

Interviewee: Nisha Gaind

That’s right. It’s not just physicists who have been recognised. There were four Breakthrough Prizes in the field of life sciences, and among the winners there was neuroscientists Virginia Man-Yee Lee and she is at the University of Pennsylvania in Philadelphia. She won a Breakthrough Prize for her work examining the way in which proteins can be tangled in brain cells, and these tangles are thought to be involved in neurodegenerative disorders such as Alzheimer’s and Parkinson’s. And then there was also a prize in mathematics and the prize here went to Alex Eskin of the University of Chicago. Now, he worked on a very interesting problem in maths called the ‘billiard ball problem’. Now, he worked on that with an Iranian mathematician called Maryam Mirzakhani and she sadly died in 2017, but they produced together a piece of work that has been dubbed the magic wand theorem, and it’s dubbed that because it very elegantly bought together many disparate fields of mathematics.

Interviewer: Benjamin Thompson

Well, Nisha, thank you so much for joining me. Listeners, to read more about these winners and more stories from the world of science, head over to nature.com/news.

Host: Shamini Bundell

And that’s all for this week. There’s just time to suggest that you check out our sister podcast Science Talk from Scientific American. You can find that wherever you get your podcasts. I’m Shamini Bundell.

Host: Benjamin Thompson

And I’m Benjamin Thompson. Thanks for listening.