Does stress turn your hair grey?
This month, mobile phones are an excellent proxy to test for Covid-19, stress and hair going grey, signs that junk food inflammes the immune system, what makes rats want to help other rats, and the emerging infections in South America linked to conquest and the slave trade. Dr Chris Smith takes a look at more of the top science publishing in eLife...
In this episode
00:37 - Testing your mobile phone for Covid-19
Testing your mobile phone for Covid-19
Rodrigo Young, UCL
Mobile phones have proved to be a powerful instrument in the fight against the coronavirus pandemic, whether it’s running apps to track contacts between people, or providing portable digital vaccination passports in some jurisdictions. Now mobile phones might be about to help us cut the cost and increase the uptake of Covid-19 mass screening: it turns out that swabbing a phone is nearly as good as swabbing the owner for infection. Speaking with Chris Smith, UCL’s Rodrigo Young explains how he came up with the idea...
Rod - What I was puzzled about was the fact that testing was so essential at the beginning of the pandemic, but at the same time, it was very invasive and also very expensive. So, it was difficult to test mass populations, which is what we needed. So some people say if we would have tested everybody every week for two months, the pandemic would be over, but we couldn't do that because it was too expensive. It was not feasible at a large scale. So I thought, how can we do this? How can we find a way to make it approachable to people? And also cheaper. That's how I came up with this idea.
Chris - And what is that idea?
Rod - Clinical PCRs are expensive because the samples taken from a person, the whole progression of that sample through the pipeline is through clinical standards, which are quite high and very expensive. You could do the same thing using reagents that have the same quality, but don't have the certification to be clinical and you could make it much cheaper. So I thought, why not using a sample that is like a readout from that person? So I thought the mobile phone is the device that we're touching and we're speaking to most of the time, there could be a very tight correlation between what we find in people's nose and mouth to what there is on the screen of mobile phones.
Chris - I suppose that's logical because of course the one place the phone does go apart from your hand is up against your face and in front of your mouth.
Rod - Absolutely. And by that time, there was a lot of evidence that SARS-Cov-2 could be detected on surfaces. So what I did was very simple. I just gathered a group of people that had been diagnosed with COVID within two days and I swabbed their phone and I did a PCR and 10 out of 10 were positive. So we then did a big study, over a thousand people, of those people that had a clinical diagnosis with a very high viral load. We were able to detect almost all of them. Now, those that were positive for COVID, but had low viral load, so they're not as contagious, those we didn't detect, which makes sense because those with a low viral load are not expelling or shedding the virus.
Chris - So this would put you sort of on par with the performance of the lateral flow tests that we've been using in some respects then, which tend to be pretty good at picking up people who are at their most infectious and less likely to pick up spurious, kind of tailenders who are probably not infectious anymore.
Rod - That's what we think. And we're doing a study comparing all three methods to see how they correspond to each other. We don't have big numbers, but so far the correlation is very, very high. It's nearly a hundred percent with lateral flow devices.
Chris - What are the implications of this? And is it that instead of subjecting people to what feels for some like a brain biopsy, which actually is arguably putting people off of getting screened, we could have a system where you run a swab over your mobile and send that off on a regular basis, and that would be as good?
Rod - That's exactly what we're doing in Chile. We're testing people that work in companies or production lines. We test them at the beginning of the week and you take out of the production line, people that test positive. This is like a prediagnostic test. So you have to confirm it with a nasal PCR and it's a much cheaper way of doing it. And it's not invasive. It's very quick to do, so, taking the sample takes around 40 seconds, less than 40 seconds.
Chris - One of the things that's frustrated our PCR tests that we've been doing, or members of the population, and particularly people who are coming into hospital is that if they've had coronavirus, they often test positive for extended periods of time afterwards. Now, do you have any feel for how the phone performs? So if a person is positive, how long does their phone stay positive? Is it fairly tightly linked to the genuine infectivity of that person? Or might their phone test positive like they might for weeks afterwards?
Rod - We have really, really interesting examples of that. In that, many times people finish their quarantine, get back to work, we test them and they're still positive. Some people when they keep on being positive on the phone, again, they're still positive on the nasal swab. And this is very frustrating for these people because they do their whole quarantine, they want to get back to work and back to normal life, but they can't because they're still shedding the virus.
Chris - Could this not backfire? In the sense that we know mobiles are mucky, and we know that they have, or they at least mirror people's microbiomes and they're covered in all kinds of horrible things. And we try and encourage people to clean their mobile phones as much as possible. Are you going to have to start discouraging people from cleaning their mobiles in order to test positive for COVID tests, with greater sensitivity and therefore potentially spread other things instead?
Rod - That was actually one of the interesting things of the study that we published in eLife. When we did this big validation study, we asked people if they had cleaned the screen of their mobile phone, but it seems that what people use to disinfect their phone might really disassemble the virus or kill the virus, but we're still able to detect the traces that are left behind. So the PCR technique is sensitive enough to still detect the traces that are left behind after you disinfect the phone.
Chris - You know, what's next for your initiative? You've got to design the app and the little gadget that will plug in the USB port on the bottom of the phone. So that the whole thing is an integrated portable screening system so that people could just plug it into their own phone and they won't even have to send you a swab.
Rod - That would be interesting, wouldn't it? What we're doing for now actually is designing a machine that will take samples from mobile phones. Like when you put a card inside an ATM, you can do the same thing with your phone. You put your phone into this machine, the machine takes a sample, and then after a few hours, you get your result as an SMS or text on your phone.
06:50 - Does stress make your hair go grey?
Does stress make your hair go grey?
Martin Picard, Columbia University
People often say that grey hairs are the result of stress. But is that true, or is it just a myth? After all, bouts of ill-health do write patterns into some parts of the body that grow. Fingernails, for instance, can develop temporary ridges called Beau’s lines that capture the timing of when an illness occurred. So, speaking with Chris Smith, Martin Picard at Columbia University, explains that he wanted to know whether hair - and specifically hair colour - does the same thing…
Martin - What we had to do first was to develop an approach where we could take someone's hair and then put it on a scanner. And then we digitized the hair into a string of numbers of how dark along the hair and the naked eye can see kind of a continuous colour across a general hair. But when you start to look at hair with such a level of resolution and precision, you see there's actually a pattern, subtle changes in the colour of the hair. And that's what we were able to quantify and then use to look at connections with stress and other things.
Chris - Because hairs grow continuously, you're therefore capturing a timeline. It's a colour equivalent of tree rings!
Martin - Exactly. The tree ring analogy is a beautiful one. You can basically get a record of someone's biological history and that's fascinating because there is no other thing in the human body that allows you quite this kind of perspective. Across time, we all walk around with our biological history attached to our head.
Chris - And can you actually marry up those colours to life events? So someone says: "I had a really stressful time last week, I had a maths test." Can you see that reflected in the colour of the hair?
Martin - We found examples of this. And we had a participant who gave a hair and her hair was dark at the tip. And then it turned white in the middle and then turned back to dark near the root. So then if you start at the tip, which is the oldest part of the hair, dark then white and then dark again. So then we wondered what happened. And because we know hairs grow at about one centimeter per month, and that hair in particular, the white segment was two centimeters. So we thought something that lasted about two months must've happened and without seeing her hair without seeing the hair pigmentation pattern that we produced, she recorded her life events, you know, over the past year. And she had just graduated, defended her PhD thesis and then went through some very stressful, personal relationship issue and then moved across the country and so on. And then that whole stress lasted about two months. And then her stress level went back down to normal. And we saw that aligning almost perfectly with the colour pattern in the hair.
Chris - Can you do this in people who are not on the verge of going grey though? Because there are lots of people who have stress, but their hairs don't go white like that. Do the colours subtly change nevertheless so you could still use this as a marker of stress?
Martin - Yeah, that is a great question. We think so. This study that was just published focused really on events of grain. It concerned to people, you know, anywhere from early twenties to late forties, fifties, where there are some hairs that are in the process of going grey. The youngest participant in our study was a nine year old girl. She had kind of a spontaneous, rare, white hair. We think it's probably more generalisable than, you know, just old people or just people that are accumulating a lot of white hairs. But perhaps just in the non-grain changes in the hair colour, we might be able to do glimpse and to decode past events of someone's biology and psychology. So that we're very excited about pursuing this further.
Chris - How do you standardise it though? Because what might be greatly traumatic for the person that you spoke about with her thesis and then personal problems and so on, someone else who's perhaps more resilient might not find that stressful at all, or might find it stressful, but not to the same degree. So how do you standardize for the individuals when you're using a tool like this?
Martin - This is a great problem in the field of psychology and behavioral sciences. What matters most? Is it what the person reports and says, this was a 10 out of 10, most stressful thing in my life, or, you know, could it be some biological marker of stress? And our studies assess both and we think both are relevant and there's actually quite a bit of data that what matters most is what the person perceives.
Chris - And how do you think that that perception of stress is translated into a change in the colour of her hair?
Martin - If we understood this, how psychological states make their way into our biology, that would be a tremendous advance for medicine. That is one of the biggest questions, I think, at this point in psychobiology, and maybe across the biomedical sciences. There's not so much known about this, but there's a few hints, including stress hormones, and those hormones evolved over millions, billions of years to help prepare the body for an eventual fight or flight response. And those hormones can have very profound biological effects on the energy within cells and on gene expression. So that's one way in which subjective experiences can be translated into biological and molecular changes in ourselves, including the hair cells.
Chris - Apart from obviously giving us an insight into something that was folklore: "This sent me grey, when I went through that!", does this also offer us therefore some kind of monitoring tool going forward for medicine, for psychology, really, to, to get some kind of life course in people and marry up the impact of distress and stress on people's health?
Martin - I think that would be beautiful. And maybe we can imagine a time in the future where you go to your doctor, you get a few hairs plucked, and then the report that comes back, you get a time course, like a little graph with a wiggling line, right? With ups and downs. And from this report, maybe your doctor could say, "Ooh, it looks like six weeks ago something happened, you know, that changed your biology, what was that?" And then maybe you could say, "Oh yes, you know, I got into this relationship. It's been very stressful or, you know, I started this new job" and maybe that might be a way to help think and be mindful of the things that we expose ourselves to and maybe a tool to direct, positive and useful changes in our lives.
13:45 - Junk food inflammation and bad behaviour link
Junk food inflammation and bad behaviour link
Tom Register, Wake Forest School of Medicine
The western diet gets a bad rap - especially if it’s the extra large duck with hoisin sauce, extra salt and no salad option. In contrast, epidemiologists repeatedly point to the cuisine enjoyed around the Mediterranean as the healthier “gold standard” diet consistent with the greatest lifespan and least ill health. But what underpins this effect? As he explains to Chris Smith, Tom Register has been studying the immune systems of monkeys eating either junk food or more Mediterranean-type diets to try to find out…
Tom - Western diets, such as eating hamburgers and cheeseburgers and French fries and Cokes and a high sugar, high fat diets is associated with chronic diseases. And one of the ideas is that the immune system is involved and we were interested in the idea that Western diets would influence circulating cells and promote disease through those.
Chris - So what was it you actually measured? What did you do? How did you do these experiments? Tell us about the study.
Tom - The study, basically, involved developing two diets, which were matched in protein, fat and carbohydrate percentages, but different in their composition. One matching the Western-like diet, cheeseburger-like diet, and the other matching Mediterranean-like diet. We fed the diet to cynomolgus macaques, which are a good model for human diseases. And these were female cynomolgus macaques of reproductive age.
Chris - And did you cross the diets over? Was this a sort of crossover thing? You feed them one diet for a period of time, then you switch it.
Tom - This was not a crossover study. That would be useful for answering selected questions that were actually raised by this study. This was a 15-month study where the monkeys consumed this diet the whole time prior to their randomization, they were eating just a child diet. And so at 15 months we isolated their blood cells and we looked at the gene expression profiles in those cells and compared between diets.
Chris - And tell me about the differences that you saw.
Tom - We saw a very marked difference between gene expression in the two diets. 40% of the genes were actually differentially regulated and the Western diet promoted a pro-inflammatory gene expression profile.
Chris - Could it be accounted for on any other basis? Did the animals change weight? Did the fat distribution in the animals change that could be causing this? So it's not the diet that's doing this. It's the second effect of the diet. What do you think is doing it?
Tom - That's a great question. And the body weights in subsets of the Western group did change, did increase over time. Their fatness increased over time, but that didn't account for the gene expression changes that we saw that was a separate kind of characteristic.
Chris - Did you make any measurements on what was living in their intestines? Because one thing that's also emerged in recent years is very important in respect of diets is that microbiome diversity is very dependent on the sort of food we eat. Did you look at that?
Tom - That's another excellent question. And yes we did. And we did find that the Mediterranean diet consumers had a greater biodiversity in their microbiome, in their gut.
Chris - So do you think then it's the microbiome that is changing what the immune system's doing or do you think that actually it's a whole raft of things that are all changing and we're going to now have to try and pick through what it is that then causes the inflammatory state in response to the Western diet?
Tom - Obviously we can't lay blame on one thing or another: it's a multifactorial. The microbiome has effects on the monocyte blood cell populations that we're studying and the microbiome has effects throughout the body, on the brain, on the heart. So yes, very definitely.
Chris - And with that in mind, were the effects just immunological or biochemical, or were there other knock-on effects of eating these diets, did the animal's behaviour change? Were there any other manifestations that went along with eating 15 months of cheeseburger-like food?
Tom - Yes. It was very interesting that we did find that diet dramatically altered behaviour. The Western fed monkeys were more anxious and less socially integrated. And we also observe relationships between the behavioural changes in gene expression, which suggests there's an interaction between diet, the central nervous system activity and circulating cell gene expression.
Chris - And is this reversible?
Tom - That's another great question. And it calls for a crossover trial. We did not do that specific study, but it's well-known that you can change your diet and you can change your risk profiles. So if you stop eating cheeseburgers and move to a more healthy diet, you can improve your health for sure.
18:59 - Key brain areas light up when rats help other rats they know
Key brain areas light up when rats help other rats they know
Inbal Ben-Ami Bartal, Tel-Aviv University
If you heard a cry for help, most likely you’d investigate and try to lend a hand to whoever had called. And if you were a rat, you’d likely do the same thing: we reported here on the eLife Podcast about 5 years ago on the observation that rats will release other rats caught in traps - even ones they don’t know - that look like they do. Now the same team that made that observation have gone a step further and identified the brain regions that are activated when the animals perform these Good Samaritan acts. Speaking with Chris Smith, Inbal Ben-Ami Bartal is at Tel-Aviv University…
Inbal - Rats tend to have kind of a bad rep, but they're really social creatures and they care a lot if they see a member of their own social group in distress. And what we find is that rats will learn to open a little restrainer, that's like a little trap, and release a cage mate or another rat from their own social group that is trapped inside. So we use this behaviour to look at what happens in the brain of these rats. What we do is actually measure which neurons were active while rats were performing this helping behaviour. And we compare that to another group that they don't care so much about. And we see the very same areas that are seen in humans that respond to other people's distress, active in rats that see a trapped rat in distress. Now, the interesting thing is that all the rats activated these brain regions, regardless of whether they actually help the trapped rat or not. But what does really predict whether rats will help or not is whether they activate a different network in the brain, which is a reward network in the brain.
Chris - Do you know what lies upstream of activating that reward centre then? Is it familiarity? This is my social group activate the reward centre, and that's the gatekeeper on whether you choose to act on this empathy signal? Or is something else then dictating what actually your behaviour is?
Inbal - That is kind of the million dollar question, isn't it Chris? We are really interested in understanding how the brain categorizes social identity of others and how that categorization determines the decisions that we make. And so what we see in this study is we see a very interesting network that connects these two systems, the empathy network in the brain and the reward network in the brain. And from the results that we find in this paper, there is an important link between these two networks that is important for helping behaviour. So in other words, when I see someone that I care about, then I act with more empathy towards that individual, and I am more motivated to help that individual in distress.
Chris - How do you know though that they're not getting that reward surge because they've helped the person, individual member of their social group that they care about, and actually the reward signal is coming downstream of the outcome, which is: "I helped them. And now I feel good about myself"?
Inbal - First of all, we still don't know all the answers, but we have a little hint that that is the case because we see that when areas in the empathy network are active in these rats, specifically a connection from the empathy network to the reward network, the more active this connection is the more likely rats are to help the trapped rats. And when we record live neuronal activity from these rats, as they're circling around a strapped individual, we see that the rewards network is active whenever the free rat is approaching the trapped rat, even before they learn to help.
Chris - So it's almost like they're anticipating how good they will feel if they help. And if that answer is big enough, because they are familiar with that social group that they're going to help, they want to do it. They're motivated to want to help.
Inbal - It's definitely possible that there is some anticipation of rewards, but since in the beginning, they don't even know that they can open the door and help, there could be another element that's involved here, an element of this motivational aspects of wanting to approach an individual that we care about when they are in distress. This very strong drive to approach with a prosocial intention is part of what we think is an evolutionarily ancient mechanism that evolved in across social species and mammalian species that had to take care of their offspring in order for the offspring to survive. So we, as mammals, developed this very strong urge to approach someone that we care about that is in distress and what we see in the reward and motivation network in the brain that is activated in these situations can be reflective of this drive to approach.
Chris - Can you mimic that effect? So if you take two rats that wouldn't normally help each other, can you inject that signal into the would-be helper to create the kind of mental effect as though they want to help, so they do?
Inbal - That is absolutely what we're working on right now in the lab. We're really interested in understanding how we can cause a shift in prosocial motivation in these rats, by stimulating those same areas. Environmentally, we can cause this shift in prosocial motivation. So in our previous eLife publication, we showed that if rats are housed for two weeks with a member of the other social group, not only do they begin to help that rat, but they know they also help strangers from the other group. And what we're trying to do now is to identify what changes in the brains of these rats while they're living together those two weeks. And can we artificially simulate that environment and cause rats to actually just really care about a rat from the other social group, even though they have no familiarity with the social group?
25:25 - Conquest, slavery and emerging infections in South America
Conquest, slavery and emerging infections in South America
Axel Solis, Universidad Nacional Autonoma de Mexico, Daniel Blanco-Melo, Icahn School of Medicine
As the world grapples - still - with Covid-19, we’re reminded on a daily basis how diseases spread. Central to this is the saying that, wherever they go, people take their germs with them. And that was equally true 500 years ago, when Europeans first landed in South America, taking with them not just their pathogens, but forced labour - slaves - and their germs too. These arrivals introduced novel viruses among the native inhabitants, causing outbreaks of hepatitis B and parvovirus infections among others. How do we know? Because, alongside historical reports that document disease outbreaks around this time, it’s now been possible to recover DNA from the remains of victims and inhabitants from that era, and not just human DNA - viral DNA too, as Axel Solis and - first up - Daniel Blanco-Melo, explain to Chris Smith…
Daniel - I've been interested in viruses for the longest time looking at ancient viruses and how those infections impacted the emergence of our human defenses. However, teaming with my dear friend, Maria Avila, we kind of teamed up to see what viruses were in circulation during this very particular interesting point in history, which is when the Europeans came and colonized America. So during that time, they not only brought themselves in of course, religion and language, but they also brought different animal species. But of course also pathogens.
Chris - Indeed. Where people go, their infections go, too - don't they? What time periods then does this coincide with - the era you're looking at?
Daniel - When Cortez conquered Tenochtitlan, now Mexico City, it was 1521 and the colony really extended all the way to 1810.
Chris - And the people who were doing that, where were they chiefly coming from?
Daniel - Well, it's famously known that the Europeans came to colonize America. However, it also coincide with this tragic period in time where the Europeans were also bringing slaves into the Americas. And those were coming from Africa. And that is what is known as the transatlantic slave trade.
Chris - Hence, your starting hypothesis is these people come, they could not just come alone, they bring with them their infections. And if they've brought people who they've enslaved with them infections that might be in those slaves may also have come.
Daniel - Yeah, exactly. Influx of people, influx of animals and influx of pathogens.
Chris - Your co-conspirator in this is Axel! So, Axel, how did you get involved in this study?
Axel - So I wanted to work with viruses. So I approached Maria and Maria told me about this project that she had with Daniel. So I decided to participate with her.
Chris - And what did she give you to do?
Axel - They obtained bones from these skeletal collections. And basically we were extracting ancient DNA and then screen for like these viruses.
Chris - The bones that Maria provided, where did she get them from?
Axel - So we got two skeletal collections. One was from an indigenous hospital in Mexico City. The other was from the south of Mexico City from, Coyoacán, a chapel. Coyoacán was one of the few Spanish settlements in Mexico City. And this hospital was treating people that died from epidemics.
Chris - Critically, these are archeological sites and therefore you must get presumably some sort of dating information that goes with the skeletons. Do you know where in the timeline they come from?
Axel - Yeah, we performed some carbon dating analysis and it suggests that these individuals survived during the first decades of the slave trade period.
Chris - And that would be what - the 1500s?
Axel - Yes. The first decades of contact.
Chris - So this is mapping onto that time that Daniel's told us is when we know that there were influxes of people from Europe and potentially bringing in other peoples from other parts of the world with them, potentially as slave labor. Do you know the individuals that you looked at the bones? Do you know whether they were Europeans or were they Africans? Asians? Can you tell us anything about that?
Axel - Yeah, so we performed the genetic ancestry of these individuals and they were, in fact, Africans. In the case of the individual from Coyacán, we found that it has a genetic composition similar to an indigenous individual.
Chris - So, Daniel, this fits the point you're making that people came from Europe, but they brought other civilization members, other populations with them. When you went through and asked, apart from human DNA, what other pathogens or viral or bacterial genetic information was in there, what did you find?
Daniel - We were able to enrich and completely reconstruct the entire genetic structure of three human parvoviruses, as well as hepatitis B virus.
Chris - Do you know if people caught these infections from the locals or did they bring them with them? Because that's the critical question, isn't it? Where they harboring these viruses when they came to the Americas?
Daniel - That is exactly the critical question and the way that we tried to answer it, when we compared the sequences of these ancient viruses to sequences that are from modern-day epidemiological analysis, what we were able to find is that the viruses belong to viruses that came from Africa. So they have an African origin, these types of viruses.
Chris - This sounds tantalizingly, Axel, then like your hypothesis, that when people come, they bring new infections with them, it sounds like that this could be the smoking gun.
Axel - Yeah, it's not the first time that somebody reported that viruses were introduced to the Americas from Africa. But this is the first time that we use ancient DNA to try to solve these questions. This is important when we consider also the context of these archeological sites. In the case of the hospital, this hospital was very important because there's an epidemic that killed millions of people in the Americas, the individuals have their body yellow and also their eyes. And they have an enlarged liver, very similar to the symptoms from hepatitis B virus. So it opens the question about the role of hepatitis B virus during, like, this epidemic.
Chris - There's also been speculation in the past that the immune systems of people who were on remote continents away from where, you know, humans first evolved, Africa, as we went further from the garden of Eden, as it were people's immune systems became less competent at dealing with the sorts of germs that were circulating in mass population centers like Europe. Does your finding add credence to that - the fact that there do appear to be these enormous epidemics or at least that there were big outbreaks potentially among the locals, which were spawned by people bringing these sorts of diseases with them.
Daniel - Yeah, absolutely. That is exactly where we want it to take now, these types of studies to really understand how the native population reacts to this influx of pathogens. However, having said that it's not like their immune system is different. It just has not been in contact with them. And therefore there is no immunity to these pathogens. So they're a bit more susceptible because their bodies are starting to learn about this new pathogen. So at the beginning of those introductions there, you see the massive decay in the native population in the Americas. And it's been documented that they are coming from these great epidemics, which are of unknown origin right now. But now that we are able to isolate viral sequences from ancient remains, now it opens a new possibility to really pinpoint which viruses were responsible.