Is the era of the cancer vaccine upon us?

Introduction to Inside Science

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1:10Download the ChatGPT desktop app today and take on your most ambitious work. Hello, I'm Tom Whipple, and welcome to Inside Science from the BBC World Service. This week, we are not looking at small questions. We are looking at big questions, such as about the biggest thing of all. Are we closer to fully characterising a black hole? And, with the launch of the Royal Society Trivedi Book Prize, we have a book about people who search for, among other things,

1:43the elixir of life, the alchemists. At Inside Science, we have no need for the Philosopher's Stone, because we have a philosopher of our own, Penny Sarchet from New Scientist. I think that's a first for me, thank you. Look, Penny, you are, like an alchemist of old, you have been scouring the most obscure texts, or perhaps just New Scientist, to bring us some of the latest knowledge. What have you found? Well, one thing I want to talk about is a new study

2:14looking at what psychedelics do to the brain and why sometimes that could be helpful. Well, that sounds like just the sort of recipe that an alchemist would have loved. But before we get to that, let's get something that's also been a long time coming. There is a wonderful, alluring simplicity to the idea of a cancer vaccine. You take your cancer, you train your body to attack it, and then, voila, your own immune system goes in and defeats it, just as if it was measles or Covid.

2:45There's simplicity to the idea, but it turns out there is a fiendish complexity to the practice. Cancer is a lot bigger than a virus, and a lot more similar to the healthy cells you don't want to attack. There is such complexity, in fact, that for decades scientists have failed.

Personalised cancer vaccines

3:01Until, we think, now. This week, Merck, known as MSD in Europe, and Moderna announced that a personalised cancer vaccine had significantly improved the outcomes of melanoma patients. Their treatment, they said, was ready for the clinic. The era of the cancer vaccine is, at last, upon us. What does that mean? We're joined by Anne Willis, a cancer cell biologist at the MRC. Thank you very much for joining us. I guess this moment's been quite a long time coming, hasn't it?

3:34There's been some false storms in cancer vaccines. I mean, there's been a lot of work in this space, and it's all been very encouraging, particularly in the animal models. But getting this to translate into humans can be a much harder, longer process. So it's very exciting that there's this breakthrough, apparent breakthrough that's come through today. Before we get into why it's exciting and why it's been so hard, I think it's important to define what we're talking about. We're not talking about a vaccine that stops you getting cancer, like you'd sort of take your summer booster shot

4:05to stop your skin cancer, are we? No, no, no, that's not how this works at all. So this is very specific. So cancer cells are very different from normal cells that contain lots of mutations. So you sequence the DNA of the cancer cell to work out how it's different from a normal cell. And then particularly for the bits of the cancer that's different on the surface of the cell, you take those bits of DNA and then you put them into the RNA vaccine and then they'll make these bits of proteins that get recognised by the immune system. So it's a way of priming the immune system to the cancer.

4:39This, I think, particularly for people who've, you know, listened to a lot of stuff about the COVID vaccines, this makes a lot of sense. You've got something that's different. You train the body to spot the different thing by sending lots of examples of it there and away it goes and attacks it. It sounds really simple. So why has this taken so long? Why has it been hard? One, you've got to have good differences on the outside of the cancer cell for one thing. Normally when they make the cancer vaccines, you pick maybe 30, 35 things that are different between a normal and a cancer,

5:1035 bits on the outside of the cell that are different. But actually we don't really know which ones of those bits are going to bring about a good immune response. And not all of the, what they call neoantigens, are actually that immunogenic. And so that's part of the issue here. It's actually working out which bits of the tumour cell are likely to give you a very good immune response and get the T cells in to start destroying the tumour. That's the hard bit. And why now? I mean, mRNA technology has been absolutely central to this. And again, we're familiar from COVID.

5:42What's it enabled them to do that's produced this apparent success? It's very fast. It's very rapid. It's programmable. So what you're doing is you're programming your own body to make antigenic responses against the tumour. So you're enhancing your own immune system to kill the cancers themselves. So that's how these things are working. I think the COVID vaccine work really has accelerated the excitement around this space. It's proved that these things can be very safe and highly effective.

6:13But this work has been going on within the cancer field for a very long time. And it is possible. This should, in theory, if you can work out which neoantigens will work for which individual, work for any tumour type. That's why it's so exciting. This is a really brilliant proof within a phase three trial that this will work. And a phase three trial, this is the final stage of testing something before you bring it to the clinic. We don't have a lot of data yet, do we? What do we know? And what do you think it means? So we know that they've done over 1,000 patients

6:44in a properly randomised trial, which is brilliant. These patients had high-end state disease with surgically removed high-risk melanoma. And there were two endpoints they were looking for. So they gave the cancer vaccine alongside the standard treatment. And there was a significant improvement in recurrence-free survival. But also what was exciting was the other endpoint was distant metastasis-free survival. And that's important, particularly to think of translating this technology to other tumour types because 90% of cancer deaths are caused

7:17by secondary metastasis, not the primary tumour. So you might have taken the tumour out, but the cancer cells were spread to other parts of the body and having tumours elsewhere. Yeah, that's the problem with the cancers. A lot of things can be treated as a primary tumour. It's spread. So what these vaccines are doing and what this vaccine is doing is it's stopping recurrence but spread. And that's what's really exciting here. So it's hard to know. They say it was significant improvement in long-term survival. So we don't know how much that is. And we have to wait to see what the data's like. So whether it's 10%, 20% or something much higher than that.

7:50But any improvement is exciting because it's kind of proof of principle of this as a way of working more generally. We've just got to get the right neoantigens. If I had a cancer, let's say I had a melanoma and I went to be treated on this. Could you just talk me through the stages and what would be going on? Well, I think what they're doing in this case is, I think it's every three weeks that people are being, you know, injected with the RNA containing their specific neoantigens. It's personalised.

8:20So they'd have, just to go back, so I'd have gone in, they would have surgically removed the cancer they could and they would have then looked at that specific cancer to see specifically to me what proteins are on the outside. Yes, that's right. They would have, they've taken the cancer out, they sequence it and then they work out what the bits on the outside likely to be that are different from a normal cell. Then they make an RNA to that and then they inject that back in again. So normally they take, so about 30 different bits that they will put the RNA in for

8:50to encode and inject it back in. So it's personalised. So it is something that's particular to your cancer. The technology is very cheap now. It's very cheap to sequence compared to what it was 10 years ago even. And actually making the RNA vaccines again is a very cheap thing to do. This is easy. The technology to do this is very fast and it's very easy to reprogram it from one person to another just to change. You just change the sequence that you're making. It's an easy thing to do. It's completely different to doing sort of big scale drug discovery.

9:21This is just re-harnessing a technology, reprogramming it, doing something else with it. How soon now do you think we might start seeing these affecting normal patients' lives? It's hard to know. It depends on what these data are like. I mean, there's a parallel trial going on for colon cancer as well, for high-grade colon cancer too. So I think as more of these things roll out, we'll get a better idea. But it's having the immunologists really understand what is and what isn't likely to give a good immune response is what's going to be key here.

9:51Are you excited? Oh, I mean, very. I'm just, you know, anything that will improve lives of cancer patients is always wonderful. And actually seeing that this extraordinary technology is sort of starting to reach its promise, this is very exciting for everybody. Anne Willis, the cancer cell biologist at the MRC.

A new star orbiting a black hole

10:10Now, time to check in with Roland Pease. You've been investigating a new revelation about a black hole, Roland. Indeed. The supermassive black hole at the Centrified Galaxy, weighing about four million solar masses, which exerts an extraordinarily strong gravitational pull if you get close enough. In 2018, a star called S2 orbiting the black hole came close enough that astronomers could detect the change in colour of its light as the radiation tried to escape that gravitational pull,

10:41a test of Einstein's theory of gravity. The Nobel Prize winning German team who measured that have now discovered another orbiting star that'll get much closer next decade, which will give another test of the theory, whether it can whip up a vortex of space-time. Here's their Stefan Gillissen. So the star S3O1 gets down to the black hole to a scale of roughly the orbit of Saturn in the solar system. Or you could also put it that the star approaches

11:13the black hole 240 times the size of the black hole. That means if you were standing on a planet around that star looking at the night sky at that moment, the black hole probably would be more or less the size of the moon we see in the sky. So it's actually coming quite close. And at this point it's going pretty fast as well. Yeah, the laws of celestial mechanics dictate that given how close we come, the speed gets very large. And in this case we are reaching a speed of something like 25,000 kilometres per second.

11:44And 25,000 kilometres per second means that within something like 10 seconds you are at the moon. And if you compare that to the speed for this Artemis mission, I mean, how many days were they on their way to finally reach the moon? Three days or something? So it's really, really fast. Or we can also express it in terms of the speed of light and it's 8% of the speed of light. So it's being pulled into the sun up to these, you know, it's accelerating. The g-forces must be amazing. Right. So the star is most of the orbit

12:14it's moving at a more reasonable speed. But the moment it's at the closest approach it has been accelerated to this extremely high speed and then gets shot around and shoots out in the other direction again. I guess this orbit is not seen best as like Earth orbit around the sun or something like that. Rather think of the cometary orbits in the solar system. Right. These comets, they for a long time reside out in the odd cloud and then by some perturbation they come in and then make a very quick short visit close to the sun

12:45and then shoot back out again. And the cometary orbit looks more like a cigar than a circle, I guess. It's absolutely, it's a very thin cigar actually. It's not a circle at all. How do you see something moving like this? Because I imagine it's a bit like a solar system. You've got all these stars orbiting the black hole but I suspect it's a lot more chaotic and you're just taking snapshots every now and again and you've got to track all these little dots of light. It's sort of fireflies in the darkness of the night. That's exactly right. So we are looking

13:16at this region over and over again and we take these snapshots and indeed I look at these images very regularly and we identify, okay, this object is not here, this object is not there. Measure the position and attract the orbits in that way. However, there's so many stars and there's in particular also bright stars and our most famous star so far which we called S2, that's the star which gave the Nobel Prize. That star is 100 times brighter than the star which we have discovered now and this is exactly

13:47the problem that in this crowded region it's incredibly hard to pick out the fainter objects. So think about trying to see a little glow warm next to the headlight of a car. You need an incredibly good optical instrument to do that. Which is what you've got with your upgraded instrument at the Very Large Telescope in Chile and at what point did you realize that this wasn't just another star that's in the system that this one was actually much more extreme than anything else you'd seen? Well, we discovered the star in March 23

14:18in one of the images and okay, there's another star not that surprising but then in the subsequent months we were quickly realizing oh, the object is moving quite fast and the fast motion always is interesting because the only way to get fast is if you're actually feeling the acceleration from a big mass so from the black hole. When's the next closest approach then? So the last one was in 23. So you actually caught it just after it whizzed past or something like that? Yeah, we just missed it so to say.

14:48It was the first observations really and the star happened to just have passed there and the period is 8.7 years so you have to add 23 and plus 8.7 so it's at some point in 2031 again. Are you able to see it at the moment it goes past the black hole again in 2031? You know, can you get that is it bright enough to be seen? Yes, it's bright enough to be seen and our interferometer is good enough to resolve it actually. But this is going to be when the gravity is incredibly intense.

15:19Will this provide a really sort of new test of Einstein's theory? Well, the black hole is rotating and it should actually rotate. Think about the universe all the objects are rotating Earth, Moon, Jupiter, the Sun, Galaxies, everything is rotating. So why should a black hole not be rotating? And the rotation of a black hole acts in general relativity a bit like a hurricane for the space-time around it. So that means it drags space and time around it.

15:50And so think about a plane flying into a hurricane and all of a sudden the pilot will not be flying in the direction he's aiming it, but there's a little extra coming from the tailwind the plane is getting and then there's a slightly different direction. And the same will happen to the star when it comes close to the black hole. It will feel that extra force due to the rotation of space-time. So what does that do? That sort of nudges its path, its orbit at that moment? It gives it a little kick, yes. So because the interaction

16:20is strongest when the star is closest to the black hole and since the star is coming in so close only for a very brief moment in time, you can think of it as if somebody would give the star a little kick like somebody hammers on the star for an instance and then the orbit has actually changed a bit and then we have the full orbit time to measure how this orbit actually has changed. So you don't need to actually observe the moment it changes its direction. It's just good enough to measure before and after, right?

16:50That's a cumulative effect. So you think you could actually measure effectively how much of a kick it gets and would that tell you how fast the black hole is spinning? That is exactly the idea and this is why we were so interested in that star because we should be able to see that extra kick it gets and then I would think we have achieved a major milestone in the direct measurement of the spin of a massive black hole. I would think that's again in the category of measuring the mass of the black hole.

17:20It's sort of a second number we can determine from the black hole and it turns out that's actually all. A black hole in astrophysics has a mass and a spin. That's all. It doesn't have any continents. There's no lakes and it has no internal structure. It's only rotation and mass and so we would then have it fully characterized and this is of course well I would think that's almost Nobel Prize worthy again if we manage to do that. I don't see why not. Black holes are rather popular with the Nobel Prizes

17:51these days. That was Stephen Gillison of the Max Planck Institute speaking for the team who detected this remarkable star S301. Details in Nature Magazine. Thanks Roland. You're listening to Inside Science from the BBC World Service. Tell us what science you think we should be investigating. Our email address is insidescience at bbc.co.uk Health care can feel complicated. That's why Optum uses technology

18:22to connect the people and processes that make health care easier, more affordable and more effective. We're making it clearer for you to know exactly what your benefits cover and to help you better manage your health we're coordinating care between your doctors and your technology. We believe better, simpler health care is always possible. That's healthy optimism. That's Optum. Visit Optum.com to learn more. Before you jump back in, you know that feeling when feedback, notes and data are coming in

18:52from every direction? ChatGPT work can make sense of it all. Turning scattered inputs into ready to review work. With your permission, ChatGPT work can gather context from apps and files, summarize incoming messages, rebuild decks and help finalize high quality documents for your team or clients. Stay in control as you move from a goal to polished work faster with ChatGPT work. Download the ChatGPT desktop app today and take on your most ambitious work.

19:24Now, it is to science writing what the Nobels are to science, what the Oscars are to film, and it's coming. Yes, I'm sure you're excited. In just a few weeks, the Royal Society will be putting out the red carpet, the science writers will be blinking into the sunlight and putting on black tie and coming for a party only marginally less bacchanalian than Vanity Fair's Oscars Bash. The most coveted prize in non-fiction science is about to be awarded.

19:54Each week before then, we're speaking to the shortlisted authors for the Royal Society's Trivedi Book Prize.

The history of alchemy

20:01And we started with Kit Chapman, author of The Age of Alchemy. The book is about how chemistry came into being. We start off with fire and we move through the ages looking at different civilizations because there's this misconception that science begins in the 18th century. It doesn't. We go into Romans, we go into the Maya and the Aztec, we go into China, we go around the world and we see how chemistry actually came into being through the Age of Alchemy. And why? Why did you decide to do this?

20:31I think part of it is addressing, again, this huge misconception that science belongs to white men in powdered wigs in the 18th century. Science is something that happens for all of us. We are constantly doing science. When we cook, when we clean, when we walk around our homes, our homes are built with materials. Science, chemistry is the science of stuff, is the science of things. And I really wanted to show how interconnected our world was and decolonise a little bit chemistry's history. Take us to some of these key parts

21:01of the evolution. Shall we go to the streets of Alexandria? The sweaty workshops of Alexandria that stink of these strange chemicals where people are claiming that they're making gold. That's really where we get the first signs of what we know as chemia. And then when that moves into Islam, we have alva, it becomes alchemia and of course alchemy. And this is a tradition that goes from the Egyptian artisans working in tombs. They were creating paints and gold. And of course, making gold is incredibly expensive because you've got to actually get

21:32the metal and mine it. And so they were looking at trying to create artificial gold. How do we make something look like gold so we can celebrate our gods? And that goes through the filter of Alexandria, which is a Macedonian Greek city. And eventually, it all conflagates together into this method of trade secrets known as chemia. One of the most arresting starts to, to be honest, any chapter I've ever read begins with the words Hennig Brand would probably be forgotten

22:02if he hadn't tried to turn his own piss into gold. Urine's got quite an unexpectedly important role in your book, hasn't it? Urine comes up time and time again. If there's one thing that is a through thread, it's urine. But Hennig Brand in the 17th century became convinced that he could turn his own urine into gold. And what happens is he collects, you know, 1,500 gallons of urine slowly fermenting in a cellar. And eventually, he actually gets something. He gets a glowing

22:33substance from his own urine. And he becomes really excited about this. He thinks he's made the philosopher's stone, this stone that is not a stone that can turn lead into gold. Of course, what he hasn't done is anything like that. He's actually isolated phosphorus. And he goes around and sells the recipe to a friend of his who actually travels Europe, showing this glowing urine to kings and queens. And eventually, it's seen by a man called Robert Boyle, fantastic scientist, founder of the Royal Society. And Robert Boyle realises what's

23:04actually happened is a new element has been discovered. When does alchemy become chemistry? And how does one make this distinction? Alchemy is a worldview of trying to understand how things relate to each other and how things work together. And the worldview will depend on who you are. Chinese alchemy, Western alchemy, Indian, Tamil alchemy are all very, very different. Alchemy brings in spirituality and religious perspectives,

23:34whereas chemistry purely focuses on empiricism and what we can observe, repeated experiment. And that's really the transition. So the last prevailing theory of alchemy is called phlegistin, this idea that there is a magic substance in everything that causes things to burn. And this slowly gets disproven once we discover oxygen, carbon dioxide, nitrogen in the air. The man who makes the leap is Antoine Lavoisier. So we have this moment that you can pretty much say alchemy ends

24:06and chemistry begins as we start looking at things rationally, as we start looking at cause and effect and looking at what makes up our modern world. What is stuff, for want of a better word? That is when we finally get to chemistry, we start thinking about atoms, we start thinking about elements, and the gold rush of the 19th century where we discover these huge swathes of the periodic table. And the periodic table itself comes about at the end of alchemy. If there's one message you want readers to take from your book, what is it?

24:38It's that everybody can be a chemist. When you look at the first chemist that we can name, the first person we can name in history that was doing something akin to chemistry, it's Tafuti Balakayim who was a Babylonian perfumer thousands of years ago. So the first chemist we can name is a woman. She was in the lower classes. She may well have been a slave because quite often perfumers were that. So it is available to everybody. If you want to be a chemist, if you want to be a scientist, you can go and do that.

25:09And I want people to realise that science is for everybody and it is a global endeavour. I'm not allowed to favourites in these books and indeed I can't because this is the only one that I've read so far but it's so much fun. Penny Sarchet, what have you brought for us?

Contrail reduction trials

25:24Well, first off, let's talk about Operation Blue Skies, the world's first trial to deploy contrail avoidance measures across an entire airspace. So this is an attempt to reduce the amount of contrails produced by planes. Why are we trying to reduce contrails? They do actually have a climate impact. They're made by soot that's released by a plane. They sort of trigger the formation of ice crystals and then result in those lines of condensation that you can see in the sky and they can last hours. And it's a little bit complicated. Some of it's good.

25:54They can reflect light during the day and slightly stop the amount of energy coming from the sun to the planet. But they're actually net bad because they also trap heat below them. And about a third of aviation's climate impact is thought to be down to these contrails. So the question then is can we reduce them? And there's going to be this new trial over the Shanwick airspace which is on the eastern side of the North Atlantic taking place this winter and the following winter. And Google AI

26:24is going to inform rerouting of flights in flight to produce fewer contrails so that it will sort of direct planes to slightly more atmospherically favourable conditions. And this does take more fuel because if you're moving up and down and changing your course then naturally you burn a bit more. But I was surprised to read that the benefits that this is likely to have are thought to kind of far outweigh any extra fuel that gets burned in flight. So if you're planning a flight over that side of the Atlantic this winter

26:55you may well be on one of these trial flights.

Brain imaging study on psilocybin

26:58Great. Anything else going on this week? Yeah. So there's this paper in Nature yesterday about what psychedelics do to the brain which I think is very interesting because there's quite a body of evidence building that psychedelics have promised for the treatment of some psychiatric conditions. And we're still figuring out how best to do this and how to do it safely. It's obviously not something you should be administering yourself at home. There is this question of like well why? Why does taking something that makes you hallucinate solve some of these difficult psychiatric problems?

27:30And so one of the sort of leading ideas of this has been the entropic brain hypothesis and this posits that psychedelics temporarily relax the organisation of your brain and they make your brain activity more flexible. but how can that explain kind of profound experiences that have long lasting effects on your sort of mindset and feelings? And so this new study sought to look at that and it's pretty cool. They did brain imaging of 62 adults before and after

28:00taking psilocybin and there were sort of two levels. They confirmed that yes, psilocybin does desynchronise brain activity which is what we thought but it doesn't just push a chaos button and make everything more random in your brain more entropic. They found that brain activity actually sort of tuned people in to their surrounding environments and they found that the stronger that this effect was in a person the more that person's mindset shifted and the more they felt life has meaning and these kinds of positive effects that can sometimes be reported

28:31with psychedelics. So there's something about if this pans out to be true that you're kind of reorganising brain activity rather than just throwing it into mayhem. That sounds slightly more promising. Thank you very much Penny, I am now after listening to that going to go and unscramble my brain but that's all we've got time for. It is goodbye from me and goodbye from you. Goodbye. You've been listening to BBC Inside Science with me, Tom Whipple. Is President Trump snubbing South Korea to reignite his friendly relationship

29:01with Kim Jong-un? I'm Asma Khaled and I host The Global Story podcast from the BBC. The US and South Korea have been close allies since the 1950s but this week Trump announced that the US will substantially reduce joint military exercises with South Korea. He cited his very good relationship with North Korea's Kim Jong-un. For more, check out The Global Story on BBC.com or wherever you get your podcasts.