Podcast: MDMA and the malleable mind, and keeping skin young

Host: Benjamin Thompson

Welcome back to the Nature Podcast. This week, we’ll be finding out how a club drug could make brains more receptive to therapy.

Host: Nick Howe

And learning about the mechanisms behind skin ageing. I’m Nick Howe.

Host: Benjamin Thompson

And I’m Benjamin Thompson.

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Host: Benjamin Thompson

First up on the show, reporter Noah Baker has been investigating how the club drug MDMA might reopen a malleable brain state called a critical period.

Interviewer: Noah Baker

Critical periods are a stalwart of developmental psychology – a period in our growth where the brain become plastic, by which I mean mouldable. The synapses and circuits are poised to change and learn new things.

Interviewee: Gül Dölen

So, I think most people are familiar with critical periods if they’ve ever tried to learn a language as an adult.

Interviewer: Noah Baker

That’s Gül Dölen from Johns Hopkins University.

Interviewee: Gül Dölen

When we learn a language as a child, we learn it without an accent. If we learn two languages, we can speak both fluently. But if we try to learn them later in life, we always struggle more and have an accent when we learn those languages.

Interviewer: Noah Baker

This week in Nature, she and her team have published a paper in which they claim to have reopened a critical period in mice using MDMA. I’ll get to the MDMA part in a second, but first, it isn’t just language which has associated critical periods, and Gül focused instead on neuropsychiatric conditions, things like depression or PTSD.

Interviewee: Gül Dölen

Mostly people haven’t really thought about things like depression in the context of critical periods, but we think that the critical period that we’ve discovered for social reward learning reflects kind of why teenagers are so susceptible to things like peer pressure and get lonely really easily, which is why they like to have 400 friends.

Interviewer: Noah BakerThey think that some form of emotional or physical trauma during a critical period when we learn how to manage social interactions could be at the root of some neuropsychiatric disorders. Critical period or not, it’s certainly known that early experiences are highly relevant to problems later in life. Here’s Sunjeev Kamboj, a clinical psychologist from University College London who didn’t work on this study.

Interviewee: Sunjeev Kamboj

So, we know, for example, that neglect and abuse are particularly potent sort of vulnerability or risk factors for psychological problems, so understanding where psychological symptoms come from often involves asking about one’s past, childhood, adolescence and so on.

Interviewer: Noah BakerGul thought that critical periods could explain why many people suffering from these conditions don’t respond well to therapy when they’re adults.

Interviewee: Gül Dölen

Because your critical period for connecting with other people in this social interaction has already closed.

Interviewer: Noah BakerHere’s where the MDMA comes in. Gül thought that if the critical period could be reopened, people may respond better to therapy. Perhaps she could even correct problems which occurred the first time around – rewire the brain. They knew that this critical period would likely be linked to the hormone oxytocin, but working directly with oxytocin is tricky, and that’s when they turned to MDMA, more commonly taken recreationally as a party drug. Their study used mice. Here’s Gül’s postdoc and first author on the paper, Romain Nardou, to take us through the experiment.

Interviewee: Romain Nardou

We placed an animal in a chamber that is divided into two compartments, and each compartment has a different bedding. And in the first day, we are measuring the time the mice spend in each bedding, and then we conditioned the mice, the mice will be with its social pair in one bedding.

Interviewer: Noah Baker

By putting a companion in one set of bedding, the mouse can begin to associate that bedding with social reward.

Interviewee: Romain Nardou

And then we isolate for 24 hours, and at the end we repeat the test in the chamber with the two different beddings and we measure the time the animals spend in the social bedding.

Interviewer: Noah Baker

When they did this test, young mice remembered the bedding they’d hung out with their mousey mate on, and they showed a preference for that bedding even after their companion had gone. But older mice didn’t do that. Spending time with their mousey peers in one bed didn’t have any lasting impact on adult mice at all and they showed no change in preference. This, the researchers say, is evidence for the critical period. The young mouse can learn from the social interaction but the adults can’t. But what happens if you give an adult mouse MDMA before the experiment?

Interviewee: Romain Nardou

The MDMA comes two days before running this behaviour, so we have done one injection in the mice of MDMA and observed that. Two days after, the mice will have the social reward learning in adult mice.

Interviewer: Noah Baker

After treatment with MDMA the adult mice show the show same kind of learning as the young ones. The researchers say their critical period has been reopened, allowing them to learn in a way they hadn’t been able to since they were young. So, could this also work in humans? Well, there are some indications that Gül’s work mirrors clinical studies being done with MDMA and PTSD patients, in particular the importance of setting – that’s to say the emotional, physical and social environment that the subject is in when it takes the MDMA. Gül found that mice that were given MDMA but then kept in isolation didn’t change their behaviour at all in the long term. Similar dependence on setting has also been seen in PTSD trials. It seems that the MDMA is facilitating the learning rather than causing the change directly. Sunjeev thinks that experiments like this have a very bright future in psychology.

Interviewee: Sunjeev Kamboj

I think it’s one of the most promising areas of development in psychological therapies, and in the combination between psychological therapies and biological treatments is this idea that you open up a period of plasticity and then provide the patient with something new, some new opportunity to learn or to experience something that’s different to what they expected.

Interviewer: Noah Baker

Gül and Romain’s work in mice is helping inform clinical studies elsewhere, and while it’s promising, it does also come with a warning. If MDMA does trigger the reopening of a critical period, that means that while under the influence of the drug, people’s brains become more mouldable and experiences during their high could be rewiring their brain, causing long-lasting impacts.

Interviewee: Gül Dölen

I think that for those people who are using MDMA, they should be aware of the fact that these are very powerful drugs and that they are opening up these windows of sensitivity to the world, and that you want to be careful who you allow into your world when your brain is in this sort of reopened, sensitive period.

Host: Benjamin Thompson

That was Gül Dölen from Johns Hopkins University. You also heard from Romain Nardou, also from Johns Hopkins University, and Sanjeev Kamboj from University College London. You can read that paper over at nature.com and if you’d like to find out even more, we have a video all about brain plasticity, addiction and phobia that you might want to check out. Head over to youtube.com/NatureVideoChannel and search for ‘Addiction: Learning to forget’.

Host: Nick Howe

Later in the show, we’ll be hearing about a glitch in the Global Positioning System – that’s coming up in the News Chat. Up next though, it’s time for the Research Highlights, read this week by Anna Nagle.

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Anna Nagle

For several years, an enormous storm has been brewing on Neptune and a team of researchers have been able to track its development. Since 2015, the team have been using the Hubble Space Telescope to photograph Neptune. In 2018, they noticed a dark spot nearly the size of Earth drifting across the planet’s northern hemisphere. Formed by a vortex of churning winds, this spot is a rarity and one of only a handful seen on the planet so far. By going back through images of Neptune, the team could see smaller clouds in the same region as the current storm, suggesting it took several years to form. Computer simulations also suggest that this storm extends deep into Neptune’s atmosphere. Head over to Geophysical Research Letters to peer at that research.

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Anna Nagle

The trusty magnetic stirrer – found in labs across the world – could be carrying contaminants that can confound chemical results, according to researchers in Russia. These stirrers – rapidly whirling short magnetic bars coated in plastic – are used when mixing chemicals and are often in service for months or years. The researchers behind this new work scanned a selection of stirrers with an electron microscope to find out how this long-term use affected them. They found that the stirrers’ plastic coating developed microscopic cracks and defects over time that could trap metal atoms and carry them from one experiment to another. Routinely cleaning the bars didn’t help – out of 60 magnetic stirrers the team only found one that was free of contamination. They recommend that fresh stirrers should be used for delicate catalytic experiments that can be hampered by contamination. Read that stirring work over at ACS Catalysis.

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Interviewer: Nick Howe

Ben, how do you think I keep myself looking so young?

Host: Benjamin Thompson

Where’s this come from?

Interviewer: Nick Howe

I know, I know, it’s amazing really.

Host: Benjamin ThompsonI mean, I hadn’t asked.

Interviewer: Nick Howe

People often tell me how young I look – some of us are just born lucky I guess.

Host: Benjamin Thompson

It could be that you’re only 27.

Interviewer: Nick Howe

I mean, okay, that could have something to do with it. But for someone like yourself, skin ageing is a fact of life, so how does it happen? Well, this week, I’ve been trying to find out, but before I get into that, I’ll start by describing how skin is structured. So, skin is divided into layers. The outermost layer is the epidermis, the protective barrier against the world. At the base of the epidermis are stem cells which use sticky proteins called collagen to secure the epidermis to the layer below. These stem cells are responsible for replenishing the epidermis by differentiating into all kinds of specialised skin cells. As the top layer of skin is the barrier between our body and the elements, it frequently receives damage by things like UV, so the cells at the top need to be restored by the stem cells at the bottom. This restoration allows the skin to regenerate itself by removing damage, which also keeps the skin looking young. But the exact mechanisms of how the stem cells themselves stay damage-free aren’t clear. This week in Nature, a new study may help clear up how the skin maintains a healthy pool of stem cells and its youthfulness. The authors of the paper weren’t available, so I caught up with James DeGregori, who has co-written a News and Views article on the topic, to find out more.

Interviewee: James DeGregori

So, what this paper has shown is when cells in our skin receive damage, that there’s a quality control mechanism where that damaged cell will downregulate one particular collagen protein.

Interviewer: Nick HoweThis collagen protein is called COL17A1 and it helps the stem cells at the base of the epidermis remain anchored to the layer below. When one of these stem cells is damaged, it produces less of the COL17A1 meaning the cell isn’t stuck as tightly, which allows its undamaged neighbours to lever it away from the bottom layer. The other healthy stem cells then divide horizontally to take up the space. Although these damaged stem cells are pushed out, they still have a role to play.

Interviewee: James DeGregori

It’s not that they die, they just lose their ability to maintain themselves as stem cells and instead they become the functional outer layer of our skin. That has a function – it still protects us – but it’s destined for eventually shedding off of our body.

Interviewer: Nick HoweThese epidermal stem cells are always in competition, and those without enough of the sticky collagen protein lose the battle and get pushed. In this way, only the fittest cells survive and by removing the damaged cells, it makes sure skin is renewed from a pool of healthy stem cells. Of course, our skin doesn’t stay youthful forever and eventually thins, wrinkles and discolours. So, after a lifetime of damage it appears that the balance between cell renewal and the rate of cell damage shifts.

Interviewee: James DeGregori

Eventually, the rate of damaged cells that accumulate outpaces the ability to purge them and eventually if your neighbours are even damaged, they’re no longer able to outcompete another damaged cell and so the damaged cells basically outpace the undamaged cells.

Interviewer: Nick Howe

Ultimately, the overall levels of the sticky collagen decline in all the stem cells and the competition slows down. So, there aren’t enough healthy stem cells left to regenerate the skin. Also, due to less attachment of cells to the layer below, the structure of the skin starts to deteriorate. The authors of the new research specifically showed that the sticky collagen COL17A1 is key to the competition between healthy and damaged stem cells. When this collagen was artificially supressed, cells were more likely to be pushed out.

Interviewee: James DeGregori

And they further showed that by restoring collagen, the same collagen, to an older, damaged cell, they could prevent the purging from happening. So, the collagen seems to be sort of the key regulator of the fitness of these stem cells.

Interviewer: Nick Howe

While this study may give a plausible mechanism for skin maintenance, most of the research was done in mouse tails, so how applicable is this to humans? James thinks mouse tails are a good model for human skin and says the authors have shown their results in more than just mice.

Interviewee: James DeGregori

They also used three-dimensional models of human skin, where they can create human skin in a culture dish, and they showed that these same processes were active even in human skin. Of course, this was done in a culture dish, but I think it’s the next closest thing to actually doing it in an animal.

Interviewer: Nick Howe

So, if we have this understanding of the mechanism of how skin is kept young, is there a possibility we could increase the amount of this collagen protein and promote the process of purging the damaged cells?

Interviewee: James DeGregori

This group actually, at the end of their paper, they screened for compounds that increased the expression of this protein, and they showed that at least with ultraviolet light-induced damage, that they could actually protect the cells and maintain better integrity of skin by treating skin with this compound.

Interviewer: Nick HoweAlthough the two compounds show promise for increasing the production of the sticky collagen, we’re still a long way from the fountain of youth. These compounds promoted wound healing, an important part of skin maintenance but not the only part. Also, these compounds would have to go through all the relevant drug testing processes before they could be used. James thinks, though, this study represents an important step forward in our understanding of how skin is kept youthful and disease-free by preventing the accumulation of damaged cells.

Interviewee: James DeGregori

I think this is a very exciting paper because it provides a specific mechanism for how youthfulness is maintained in terms of this purging of damaged cells, and I think this could be very useful because not only is damage to cells a factor as we get older, but it’s a factor when we get exposed to, for example, ultraviolet light, which many of us are exposed to even on a daily basis. So, if we can have some way of improving this elimination, that could be useful for prevention of skin cancer and eventually it could be useful for the long-term maintenance of what’s a very important barrier between us and the outside world.

Interviewer: Nick HoweThat was James DeGregori. You can find his News and Views article and the original research paper over at nature.com.

Interviewer: Benjamin Thompson

Now, it’s time for the News Chat, and joining me once again is Nisha Gaind, European Bureau Chief here at Nature. Nisha, thanks for coming back.

Interviewee: Nisha Gaind

Of course, hi Ben!

Interviewer: Benjamin Thompson

Well, for our first story today, let’s head to Iran, and quite troubling news for a group of conservation researchers.

Interviewee: Nisha Gaind

Yes, this story is about a group of eight researchers who are on trial on charges of spying. The researchers maintain their innocence but they are now being tried in one of Iran’s revolutionary courts, and there are some concerns being raised because we’ve heard reports that their legal rights are being denied.

Interviewer: Benjamin Thompson

What’s this group on trial for then in the first instance?

Interviewee: Nisha Gaind

So, these people are all scholars. They are conservation researchers who study things like wildlife. In particular, some of them were studying an endangered species called the Asiatic cheetah in national parks in Iran, and they seem to have gotten into trouble because they were using camera traps, which are a very standard piece of equipment for researchers to use, but they have been accused of spying on sensitive military infrastructure and they were arrested last year in January 2018 and they have been detained since and have only just gone on trial.

Interviewer: Benjamin Thompson

And there are some concerns about how this trial is progressing.

Interviewee: Nisha Gaind

That’s right. The trial is taking place in on of Iran’s revolutionary courts and this is a court that is quite secretive in the way that its trials happen – there isn’t much information available. What we do know is that in one session, the whole group of researchers was read a very long indictment and some of these charges include the charge of sowing corruption on Earth, which can actually carry the death penalty. And what we know after that is that two of the researchers have had hearings for their trial, but we don’t know much more than that. Sources close to the researchers have told Nature that some of them are having health problems because they don’t seem to be receiving proper care in prison and there have also been concerns over whether they can properly access legal representation and whether they have proper counsel.

Interviewer: Benjamin Thompson

I have to ask why are researchers being tried under this court system?

Interviewee: Nisha Gaind

This is a development that we have been seeing in Iran for a year or so. There appears to be a kind of crackdown on environmental researchers. Now, environmental research used to be this sort of apolitical space in Iran. It now appears to be becoming quite politicised and there appears to be a lot of attention on Iran because it’s got some environmental issues that both western politicians and NGOs are focusing on, and that’s a concern for the Iranian authorities. According to some, there are fears that what seem to be quite innocuous environmental-monitoring activities are in fact covers for spying or espionage or some other type of infiltration that the authorities see as a security issue.

Interviewer: Benjamin Thompson

Presumably this has caused outcry outside of Iran?

Interviewee: Nisha Gaind

Yeah, it’s caused outcry not just in academic circle but also in the international community – the UN has weighed in, Amnesty International and several other wildlife organisations as well, including WWF, who are urging the Iranian authorities in public statements to ensure that these eight researchers are given a fair trial and there are also some researchers who have experienced this scrutiny of the Iranian government, a couple of Iranian researchers who have left Iran because of it, and they say as well that this is being unreasonable politicised and these researchers should not be treated in this way.

Interviewer: Benjamin Thompson

Obviously, it can be very difficult to get information out about what’s going on with these researchers – what happens to them in the near future?

Interviewee: Nisha Gaind

So, that’s a very good question. We don’t know very much and it is very tough to get information out about these cases but we think that these hearings will continue for these researchers and hopefully we’ll have an update soon.

Interviewer: Benjamin Thompson

Well, let’s move on to our second story today, Nisha, and well, it’s one that maybe I think affects me. It’s about GPS receivers – I can get lost in my own house and without the blue dot I’d never find my way around – what’s going on here?

Interviewee: Nisha Gaind

Yes, this is a story about something that sounds quite dramatic. There is a glitch in the Global Positioning System. Now, thankfully this isn’t going to affect newer devices like your phone, but it is going to affect older data loggers which include thousands of scientific instruments and they could malfunction this weekend.

Interviewer: Benjamin Thompson

Which sounds very worrying. Why is this happening in the first instance?

Interviewee: Nisha Gaind

So, GPS is ubiquitous – we all know it as this navigation technology that allows us to track where we are – but GPS receivers also function as ultra-precise timekeepers because they are synchronised with these GPS satellites that are circling the Earth. And these receivers are embedded in many scientific instruments – in radio-telescopes, in seismometers, in detectors that do all sorts of things across research – and they use this time-keeping ability to time-stamp data that they generate with nanosecond accuracy. The glitch is down to something called the GPS ‘week number rollover’, and this happens because of the way that the signal is broadcast. These signals include a ten-digit ‘week number’ in GPS time, which began in January 1980. But because ten digits covers only about a thousand weeks, which is about 20 years, this limit gets reached every 20 years, and this is going to happen for the second time on the 6^th April, and at that time, the clocks on GPS satellites will roll back to week 0, and there’s a risk that when that happens, receivers won’t know what to do with this information, they’ll think that time has started again, and it could really mess up data streams.

Interviewer: Benjamin Thompson

You say this is the second time this has happened, so presumably it’s something that can be addressed?

Interviewee: Nisha Gaind

Luckily, in this instance it’s actually older receivers that are affected and manufacturers are on top of the problem. They have put advice out on their websites and if you’re a user of one of these receivers, you can go to the website, download a firmware update, or even buy new equipment that won’t be affected by this anymore.

Interviewer: Benjamin Thompson

Do we know any fields that might be particularly affected by this glitch?

Interviewee: Nisha Gaind

So, one field of research that is particularly affected is seismology because seismologists tend to have a lot of these receivers out in the field. Researchers have to go and get these recorders, bring them back into the lab and update them, and they’ve been doing it for hundreds of recorders. It also affects a neutrino experiment which use GPS to kind of synchronise their particle beams and their detectors, and it also affects receivers in places like Antarctica which might even be embedded in ice sheets. So, yeah, it affects recorders all over the world.

Interviewer: Benjamin Thompson

Well, thanks for joining me Nisha. Bit of a public service announcement there – maybe time to check scientific equipment before the weekend. Listeners, you can find out more about this story and more from the world of science over at nature.com/news.

Host: Nick Howe

That’s it for this week’s show. Don’t forget to give our sister podcast a listen – that’s Science Talk from Scientific American. Find it wherever you get your podcasts. I’m Nick Howe.

Host: Benjamin Thompson

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