In the news this week: mRNA vaccine giants Moderna and Pzfizer face a legal battle over potential technology infringements, and a new study explains how small talk with strangers before working together can improve strategic interactions. Plus, we hear about research suggesting cannabis use doesn't impact an indivduals motivation, the biggest animal alliance outside human beings, and the hot take on cancer risk in coffee drinkers... 

A clash of the Covid-19 mRNA vaccine titans Pfizer and Moderna has sent shockwaves through the pharmaceutical world this week. US company Moderna has filed claims against its rival in both America and Europe alleging that patents relating to key components of the mRNA vaccine technology - which was used for the first time clinically and has proved game-changing during the Covid-19 pandemic - have been infringed. With huge revenues at stake from the technology, there’s a lot riding on the verdict. Clare Bryant is an immunologist at the University of Cambridge and has also worked previously in the pharmaceutical industry herself. As she explains, it’s not altogether clear who owns what…

Clare - Basically, we've done the massive world clinical trial using a new technology, the mRNA vaccine technology, and shown that this technology is great for making vaccines. So we're now at the point that this technology's been invested in and companies are saying, "okay, how can we use these kinds of technologies to make new vaccines for other diseases," for example, HIV, which would be the holy grail. This now has been triggered because we are not in the pandemic as it was before. So the ethical issues around making vaccines to treat the world, to protect everybody against a pandemic disease, have gone into the background. And we're now moving forwards, looking very closely at the technology, looking at who owns what, in order to trial up new vaccines for other diseases, and to make the big money that's really out there if we can use this technology more widely.

Chris - And what's at stake? What are they arguing over? What's the technology that one says the other has nicked?

Clare - To make the mRNA vaccine work - which is a way of introducing mRNA into the cells of your body to make, in this case, the spike protein from the COVID virus, and then you can make an immune response against it - that immune response is there onboard in your body to tackle the next strain of virus that comes along. So to do that, normally mRNA and cell is made just when you need a protein, the mRNA is then broken down and it disappears. So you've got to do a number of different things. You're introducing a foreign RNA. A foreign mRNA is what you see if you get, for example, a virus infection on board. So the body makes an immune response against the RNA in its own right and that makes you feel really sick. That's called toxicity. Two scientists made a really neat discovery, which was that the coding sequence, the nucleic acid coding sequence for the mRNA, they could change one of the nucleotides and chemically modify it. And what that did was then two things: it decreased the toxicity (you didn't feel so rubbish when you have the vaccine), but the other thing it did was make the translation of proteins much more efficient. So you're generating a molecule that makes the proteins against the virus much more efficiently, much more of it. And people don't feel as sick when they get this modified messenger RNA.

Chris - Now, who did that? Did Moderna do that? Did Pfizer do that or did someone else make that crucial step?

Clare - Two scientists, Weissman and Kariko, did this around the mid 2000s. And this was actually done six years before Moderna picked up the technology that they then patented themselves. So this is part of the controversy that's going on, which is that this discovery was made and patented, in fact, before Moderna came in, so there's already complexity around that patenting as well.

Chris - And is that what Moderna say Pfizer have copied - it's that crucial modification of the genetic message that they're alleging that Pfizer are copying.

Clare - So there's three things actually. That's one of them and that's absolutely crucial. They're also arguing that the way in which the messenger RNA is packaged up into a lipid particle is a Moderna discovery. And then finally, they're also arguing that because Moderna made some vaccines against MERS, which was a similar virus to COVID 19, that they used in the MERS vaccine, full length, spike protein. They used a similar approach to make their COVID 19 vaccine, which was the full length spike protein, and Pfizer did something very similar. So it's the modification of the messenger RNA., it's the lipid particle wrapping up to make it go into cells efficiently, and then it is also the full length spike protein that they've used for their vaccine. So there's three elements to it. And it seems to be really murky. There's a lot of discussion amongst the lawyers as to what's valid and where this is going to go. It's interesting and complicated and big bucks involved and that's the reason for the problem.

Chris - They must have a reasonable chance of success to their mind because otherwise they wouldn't have launched into this in the first place. Or is it a question of damned if they don't damned if they do?

Clare - These things are never straightforward. The patent lawyers certainly think there is a decent case to be answered here. I think it's going to be really interesting to see how this comes out in the wash because Moderna had been working on this for a long time. They've made MERS vaccines, which was successful. The whole strategy was in place. So it's reasonable, but Pfizer argues that they too have had this kind of program going on for a long time. And the difficulty for us as outsiders is we don't know what the companies have been doing, how long they've been working on it and what the intellectual property right position is behind all this, because it's all wrapped up in secrecy. So the lawyers, certainly the media releases from all the lawyers, suggest that they have cases, but we will wait and see exactly how this all pans out.

We’ve all heard the old saying that first impressions matter, or that there’s no second chance at a first impression. But what does the science behind first interactions say on the subject? A new study ran an experiment which found that subjects engaging in small talk with other people formed impressions about their personalities that then appeared to influence their behavior when playing strategic games. Julia Ravey has been talking to Daniel Sgroi, of the University of Warwick, about how early interactions shape future opinions, and why the brain decides to judge people on the first impression they make.

Daniel - I think actually it's a natural thing that we do. We tend to do that so that we can use those impressions later on in life. So even a short conversation or a brief interaction can give us a little bit of insight, which we can then use later on to benefit ourselves and also to benefit the sort of group interactions we have with other people. So it's almost an evolutionary advantage that we have as humans

Julia - And what elements contribute towards this first impression of a person?

Daniel - If we are thinking about talking, it's to do with the words that we use, to do with the rapidity with which we speak, the amount of information that's contained and, fundamentally, it's to do with the sort of personality of the person that's speaking and how easily we can determine the personality of that person through the words that they use.

Julia - How big a role then does small talk play in forming that initial first impression?

Daniel - A very big role. I think our own research suggests that even very short bursts of small talk, maybe talking for two minutes with someone you've never met before, can give you a decent stab at guessing the sort of personality of the person you're talking to. And in future, that helps you to understand them, helps you to form a mental model of the sort of person that they are, and which in turn helps you to interact with them better.

Julia - Are there any specific traits of a person's personality that are particularly susceptible to be picked up in this initial small talk?

Daniel - Yes, absolutely. So one of the big traits that's been identified by psychologists over the years is how extroverted people are. So how much they talk, how outgoing they are, how much they enjoy interaction with others. And that trait, as you might expect being the trait that really is about interaction, is the one that comes through first. So even in a short burst of small talk, you can often detect whether the person you're talking to is an extrovert or an introvert.

Julia - And with this initial small talk, how prolonged can the effects of that influence be?

Daniel - They can be pretty prolonged. In our own experiment, you talk for two minutes and then maybe admittedly within about an hour or so, these sorts of impressions are sustained. It seems likely that within the workplace, since you don't talk to someone once then interact with them and never speak to them again, more likely you are gonna be talking to them on a repeated basis. So as long as you, as long as you keep that small talk going, talk to someone a little bit every day, you can generally form lasting and quite accurate impressions of the sort of personality of the person you're interacting with.

Julia - And in your experiments you've recently just published, you looked at how small talk impacts strategic interactions. So what did you find there?

Daniel - Well, we found that in the sort of strategic interactions we were looking at, which were the sort of situations where cooperating and coordinating well with others improves, improves everybody's wellbeing. In those sorts of situations, a little bit of small talk can really have a dramatic effect in how well you form beliefs about the personality of the person, which feeds into your understanding of how they're gonna behave in those sorts of interactions, which in turn makes it easier for you to coordinate and cooperate with them. If you don't have that small talk, which was in the placebo setting, you don't see any of those benefits. And so generally speaking, the groups do a lot worse if they don't get to have a couple of minutes of chatting with each other at the beginning

Julia - How do you think this work could extend outside of the lab? How could it apply in the real world?

Daniel - I think one of the things that we showed in our research, we use a sort of standard experimental design in which the only difference between our two settings is whether people get to communicate or not. And the benefits that are obtained through that communication are quite sizable for the individuals and for the groups. So I guess what we're showing is that people might think small talk is irrelevant, maybe a drain on productivity, maybe it doesn't fulfill any sort of social purpose over and above, perhaps just a normal chat with someone, just a bit of social lubricant, if you like. But what we see is it actually fulfills an important purpose in terms of efficiency, wellbeing, and improvement. It just makes groups work better together and I think the sort of further point really is that any managers out there, any people who are thinking, 'well, I want to stamp down on social interaction of this sort, I don't think it's good for productivity'. Perhaps our research is telling them that's not true, that this sort of small talk actually is very good for productivity.

Julia - So do first impressions count?

Daniel - Yes, they do, which can be a bad thing and it can be a good thing. All I would say is if it's the first time that you are interacting with someone, even if they've just asked you how you are, who you are, how you're settling in at work. I think it's important, in that very first impression, to try and reveal as much about your personality as possible. Don't just respond with the standard 'I'm fine. Thanks'. Try and say a little bit more, give them a clearer idea of the sort of person you are, help them to better understand how you are gonna behave when you interact with them in the future. And you'll be able to coordinate and cooperate better with them when you do interact with them.

People under the influence of cannabis are often regarded as lazy, laid-back and apathetic. But is this a fair assessment? Cambridge University's Martien Skumlien has just published a study, in collaboration with UCL in the International Journal of Neuropsychopharmacology, comparing how frequent cannabis users fare against non users in a series of tasks designed to probe this.

Martine - There's this idea that cannabis will make you lazy and demotivated and apathetic. So think of like The Dude in The Big Lebowski, for example, that's basically what we sought to find out in this study. So we compared people who use cannabis and people who don't use cannabis on a few different assessments of reward and motivation. So they completed a questionnaire with questions like 'I have initiative', 'I get going during the day'. And then they also did a laboratory tasks where they could do these button presses to get chocolate or sweets. So kind of a measure of if you're willing to expend physical effort to get a reward.

Julia - And so what did you find then from these tasks?

Martine - Well, we basically found no difference between people who use cannabis and people who didn't. So really no evidence to support this stereotype of the like demotivated cannabis user.

Julia - So if it's not the drug that's causing this sort of stereotype, what do you think has perpetuated that?

Martine - That's a good question. And I'm not really sure. So I should point out that the people in our study were not under the influence of cannabis, so they were quote unquote 'sober' when they did the tasks. It could obviously be that people are slightly less motivated whilst they're high. So maybe that's why you get this trope. I think also anti-cannabis public safety adverts, particularly in the 90's, but today as well, really, really played up this trope, that cannabis is gonna make you super lazy and take away all of your ambition and you're going to fail at school. And so maybe it, it kind of comes from there as well.

Julia - Do you think that the idea that cannabis uses are apathetic could come from the fact that many people use cannabis as self-medication, if they have other mental health problems?

Martine - I think that could partly be the case. So it could be that cannabis has like an indirect effect through, say, depression or psychosis or something like that. Or, for instance, if you have people who have very strong cannabis use disorder, maybe they would show a stronger effect, but this is still the minority of users and obviously most people who have depression, presumably don't use cannabis. So I don't think it can, it can be the whole story.

Julia - So you think the findings from this research could have any baring on legal standards towards cannabis in the UK?

Martine - So one of the things that I hear quite a lot in this debate is that people are worried about adolescents particularly. So if we legalize cannabis, then adolescents are gonna use more cannabis and adolescents maybe are more vulnerable to harmful effects of cannabis. So we also looked at this in this study. So we did compare cannabis users who were adults and cannabis users who were adolescents and basically we're not finding any adolescent vulnerability effect, though so I guess in that sense our results are somewhat encouraging. Although we have only looked at motivation, there are obviously a bunch of other psychological and cognitive outcomes that people need to assess. And I should just add that obviously we're scientists so our mission is to find the answer and then it's up to other people and policy makers to decide what to do with those.

With millions of cups of coffee being quaffed down daily, we’d like to think that one of the world’s most popular beverages isn’t slowly killing us. And as a coffee drinkers at the Naked Scientists, we're more invested than most. So that’s why a paper in the journal Clinical Nutrition caught our eye this week: the authors had used the clever trick of linking genes that make people hooked on caffeine with cancer outcomes. Moreover, reading the author list, Chris Smith discovered that one of the authors works down the road from him, so he invited him along for a chat over… you’ve guessed it… a coffee…

Barista - What can I get for you?

Chris - What do you want, Steve?

Steve - Hey, can I get a medium latte, please?

Chris - Yeah, I'll have the same.

Barista - Anything else for you?

Chris - That's all. Thanks.

Barista - So that's 3 45, please. Thank you.

Chris - Should we go outside?

Steve - My name's Steven Burgess. I'm a program leader at the MRC, the Medical Research Council biostatistics unit at the University of Cambridge.

Chris - Now the irony won't have escaped you, Steven, that we've brought you to a coffee shop, and we're gonna talk to you about a paper that you've just written, linking the stuff in that cup with cancer.

Steve - Firstly, thank you very much for buying me the coffee. It's very much appreciated. So obviously a lot of people in the world drink coffee. It's quite a common drink. So we really want to know from a health point of view is coffee good for you? Particularly with relationship to cancer? There's been a lot of studies out there and we really wanted to bring some clarity to that situation.

Chris - I read somewhere that more than a billion kilos of coffee gets drunk every year. At that level of consumption, surely if it was killing people we'd know wouldn't we?

Steve - Yeah. So certainly if coffee was similar to cigarettes, then yeah we would learn about that pretty quickly. But it could well be that there is a small harmful effect of coffee, which would be really difficult to pick up. I mean, really when you want to do these studies in a scientific way, you'd really like to do a randomized trial, but to do a randomized trial of coffee consumption, particularly for an outcome, which takes a long time to develop like with cancer its gonna be pretty much impossible. We can't randomize ourselves but the idea is that we try to use naturally occurring factors, which act a little bit like randomization. So in our case, we were looking at genetic variants and there are some genes which influenced the amount of coffee that you drink.

Chris - So how did you use that information to marry up the likelihood of having cancer from drinking coffee then?

Steve - People went into a questionnaire. They were asked how many cups of coffee do you drink? So we link the coffee consumption to certain genetic variants and then we see 'do those same genetic variants associate with risk of diseases'. In this case, we were looking specifically at cancers.

Chris - How many people did you consider and where did you find these people?

Steve - So this is data from a study called UK Biobank with about half a million participants in.

Chris - And what did you find?

Steve - When we looked in the overall analysis, there was no association between having a genetic predisposition to drinking more coffee and having cancer, which obviously is aa good finding for me as a coffee drinker. But when we looked specifically at cancer subtypes, we found a particularly strong association for something called oesophageal cancer.

Chris - How could it be present when you look at the oesophagus but when you look at all cancers, you don't see an effect? Is it just that it drowns out the effect of the oesophagus and it's only when you look specifically at that one that you see this association?

Steve - So our theory and it's a theory, I mean we can talk about the evidence supporting it, but our theory is that the link with oesophageal cancer isn't due to the coffee per se, isn't due to anything in the coffee or the caffeine, but due to thermal injury, just from drinking hot liquids. I mean we know that hot temperature can, can cause cancer. We know about skin cancer and if you're putting 70, 80 degree liquid down your throat, then really is it that big surprise that that's leading to greater instance of cancer in the throat?

Chris - How did you dissect out the temperature effect then? Did you actually have data from the participants on whether they like it or like it cold?

Steve - We did actually have some data yes. So UK Biobank asked a whole load of questions and one one of those questions was 'what temperature do you prefer to drink your hot beverages at'. Coffee consumption was associated with a greater change in cancer risk for those people who had a preference for hot or very hot.

Chris - How much then has my risk of esophageal cancer changed by quaffing down a few coffees every day compared to if I didn't drink coffee at all?

Steve - Yeah, that really is the $64,000 question. So when we compared people with a genetic predisposition for drinking 50% more coffee, we saw, in the warm group, we saw about a two and a half fold increase and in the hot, very hot group, we saw a four, five fold increase.

Chris - So presumably then if you switch the study round and you said rather than coffee, what about tea? Since both are beverages usually drunk hot, you ought to see a similar trend then, or even hot chocolate.

Steve - Yeah, so we didn't have quite as granular data from the study on tea drinking as we did for coffee drinking. But certainly the genetic score, we know from other data, that the genetic predisposition to drink more coffee also gives you a predisposition to drinking more tea and when we restricted the analysis to those people who reported that they didn't drink any coffee, we still saw an association with cancer. So that's, again, that's one of the lines of evidence which led us to believe that this thermal injury hypothesis, that it's really the hot liquid and not something specific to coffee.

The development of alliances was a behavioural leap forward that helped humans become the dominant species on earth. Alliances are not uncommon in nature, occurring in lions, horses and primates such as chimpanzees. However, a much more rare occurrence is a step above simple alliances, which is to say alliances with other alliances. For a long time, this method of sharing and communicating was thought to be unique to humans - something that put us above the rest of the animal kingdom. However, a recent study has found that one other group of animals is now displaying this behaviour: the population of bottlenose dolphins in Shark Bay, Australia. Will Tingle has been talking to Stephanie King, of the University of Bristol, and Richard Connor, of the University of Massachusetts at Dartmouth, about why these alliances need to exist, and how they may have come about.

Stephanie - As a male dolphin in Shark Bay, what's really important is to find females to mate with so you can have lots of offspring, you can pass on your genes. But it's a population where there are lots of animals, right? So the density's really high. It's a big population. And each year there are only a few females available to have offspring because many of them already have calfs that they tend to look after for a number of years before that calf becomes independent. And so you have all these males competing for just a few females. So as a male dolphin, in order to get access to females, you need to form these alliances. You need to work together to find females that are ready to have offspring, to mate with. You need to keep that female with you, and you may need to impress her to mate with you. But to do that, you have to work together. You have to work with other males in order to secure access to that female and to defend her if rival alliances come in, rival males come in, and try to take her. And as a male dolphin in Shark Bay, if you are not in an Alliance, then you secure few, if any paternity. So you sire few, if any, offspring

Will - And this, as you say, is remarkably complex behavior. Do you think there are environmental factors behind the development of this or did it just sort of happen?

Richard - Well as Stephanie was saying, there is a very high density here and it may be as simple as, if you're going to run into your enemies you better be with your friends. So they have these pairs and trios. They go around, the males, go around in pairs and trios to form these consortships with individual females. But that's not enough for them because two pairs or trios can take a female from them. So they have these second order alliances of four to 14 males that we've learned over the years are the core social unit of the male dolphins. They're basically lifelong commitments and it's within these groups that they formed the pairs and trios. And then the more recent discovery is that these second order alliances have relationships with other second order alliances to form third order alliances, and then males bonds with their third order allies are really important for their success.

Stephanie - And it's this 'between group', this between alliance cooperation, that's so interesting and so exciting because typically in the animal kingdom social birds and mammals will interact within their groups, and interactions between groups are hostile. So you are in competition with other groups and the interactions between groups are competitive. There is conflict, they are hostile. And yet here, we're seeing that the dolphins in Shark Bay are behaving strategically while it's in their benefit to form these cooperative relationships with other alliances. So we have this between group cooperation, and that is something that we only see in our own society, so in humans.

Will - Is there something about Shark Bay that allows these dolphins to develop their behavior?

Richard - There's two reasons probably that the dolphin society here is so much more complex than other places where they've studied bottlenose dolphins inshore. So Shark Bay is really a marine biologist paradise. It has the largest seagrass beds in the world and those seagrass beds support a lot of everything. We see tons of dugongs out there, lots of sea turtles, and lots of dolphins. That combined with their slightly smaller size means that again, they're a higher density. And so they're bumping into each other a lot and they need to maintain these complex relationships. And so if there is damage to those seagrass beds from climate change events, yeah I mean we'd hate to watch this incredible society become simplified and see the damage to the bay over the next few decades

Stephanie - Protect your marine sea grasses, protect your marine environment.

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