Archaea

Misha Glenny and guests discuss one of the most remarkable scientific discoveries of the 20th century: the archaea microorganisms. In the 1970s the American microbiologist Carl Woese (1928-2012) realised that the tiny bacteria-sized organisms he was studying were not actually bacteria but from an entirely different branch of the tree of life. It became clear that archaea, as he named them, share aspects of the cells in all plants and animals even if they often live in places where other life struggles including salty lakes, acidic pools, under the sea bed and in the gut. While aspects of what followed from Woese are still under debate, further discoveries suggest that life on Earth has been on a journey of separation and reunion: that the first cells developed into bacteria and archaea billions of years ago and that some of those later combined to form the complex cells from which we are made. With Christa Schleper Professor of Genetics and Microbiology at the University of Vienna Thorsten Allers Professor of Archaeal Genetics at the University of Nottingham And Buzz Baum Group leader at the MRC Laboratory of Molecular Biology in Cambridge Producer: Simon Tillotson Reading list: John Archibald, One Plus One Equals One: Symbiosis and the evolution of complex life (Oxford University Press, 2014) Buzz Baum, ‘I’: A Biography of the Biological Self (Allen Lane, forthcoming 2027) Franklin M. Harold, In Search of Cell History: The Evolution of Life's Building Blocks (University of Chicago Press, 2014) Nick Lane, Power, Sex, Suicide: Mitochondria and the Meaning of Life (Oxford University Press, 2005) David Quammen, The Tangled Tree: A Radical New History of Life (Simon & Schuster, 2018) Jan Sapp, Evolution by Association: A History of Symbiosis (Oxford University Press, 1994) In Our Time is a BBC Studios Production Spanning history, religion, culture, science and philosophy, In Our Time from BBC Radio 4 is essential listening for the intellectually curious. In each episode, host Misha Glenny and expert guests explore the characters, events and discoveries that have shaped our world.

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  This is In Our Time from BBC Radio 4, and this is one of more than a thousand episodes you can find in the In Our Time archive. A reading list for this edition can be found in the episode description wherever you're listening. I hope you enjoy the programme. Hello. There are some scientific discoveries that seem to change everything. And one of these is that of the Archaean microorganisms. It was Karl Woese who, in the 1970s, realised that the tiny bacterial-sized organisms he was studying were not actually bacteria, but from an entirely different branch of the tree of life.

• 2:28Speaker 04

  And excitingly, those Archaea, as he called them, share aspects of the cells in plants and animals, including us, indicating that it was Archaea, in combination with bacteria, that made complex life possible. Well, with me to discuss Archaea are Christiau Schleper, professor of genetics and microbiology at the University of Vienna, Toastan Alice, professor of archaeal genetics at the University of Nottingham, and Buzz Baum, group leader at the MRC Laboratory of Molecular Biology in Cambridge. Buzz, let me start with you. Until Woese, scientists had been looking at Archaea through microscopes, but not seeing them for what they were.

• 3:13Speaker 04

  So what exactly are they, and how widespread?

• 3:16Speaker 05

  Yes, so Archaea are a kind of cell. And of course, every living thing on Earth is actually made of cells, so everything's cellular. But the things that we're used to, which are made of cells, are big things like plants and animals. And Archaea are small cells, and the cell is the organism, and the organism is the cell, so the single-celled organisms. And they are wonderful, in a way, because there are things that they share, as you sort of pointed out, with us, and there are also things in which they share with bacteria. And there are other ways, they're completely otherworldly. And so it's as if one has sort of come across an organism from another planet here on Earth in many aspects of their biology.

• 3:58Speaker 04

  So until that point, they weren't recognised. People thought that they were bacteria. Is that right?

• 4:04Speaker 05

  Yes, so down a microscope, especially a light microscope, where the resolution is not very good, Archaea can seem to look very similar to the other very small organisms that we know about, which are bacteria. And so everybody had conflated the two and treated them the same. And then Carl Woos, one of the things he enabled us to do is to look at them through a different lens, through the lens of molecular biology, and suddenly, by teaching us that there are these separate organisms, we could then look to see where, which of these things we thought were bacteria were archaea, and suddenly the sort of scales fell away, and looking at life after Woos, it looks different, and there are archaea everywhere which are extraordinary.

• 4:44Speaker 04

  We'll come to Woos's research a little bit later, but before we do, some of these archaea are called extremophiles, so what sort of extreme environments do they live in?

• 4:56Speaker 05

  I mean, of course, we call them extremophiles, and they think we're extremophiles, because each organism is accustomed to living someplace where it's happy, but it is amazing that archaea really can live, you know, what lives in the Dead Sea, archaea in abundance, in salt crystals, what lives at the bottom of wells, oil wells, at the bottom of the sea, in volcanic springs, the cells we have in the lab are from Yellowstone National Park, they grow at 75 degrees centigrade, we have other ones from the bottom of deep-sea vents that grow at 90 degrees on hydrogen gas, and there are the ones that Krista Schleper and myself work on which grow without oxygen and live quietly, so they live in these extraordinary,

• 5:38Speaker 05

  different environments, but of course, they've been on planet Earth for a long, long time, and so they've also evolved to live in all kinds of niches, and probably all niches as the Earth changed, they've been changing with the Earth, and they really live everywhere.

• 5:53Speaker 04

  Okay, in order to understand the difference between us, bacteria, and archaea, there are some basic terms we're going to have to understand. So Torsten, Alice, can you explain to us what prokaryotes and eukaryotes are? Can you define those for us?

• 6:11Speaker 06

  Yes, with pleasure. Let's start with eukaryotes, that's us. So we humans, we're all eukaryotes. And eukaryotes comprise animals, plants, fungi, and some larger microscopic organisms like amoebi. And all of our cells are on average large, about a tenth of a millimetre across, and they have all of these complicated internal structures, which include the nucleus, that's where our DNA resides, and then mitochondria, which we use to generate energy using oxygen to power our metabolism. And if you're a plant, you have chloroplasts.

• 6:51Speaker 06

  And the chloroplasts use the energy of the sun to make sugars and energy for the plant to grow on, but generate oxygen as a by-product. Prokaryotes, on the other hand, they comprise archaea and bacteria. They have no complicated internal structures. And much as it's unsatisfactory to do so, they are defined in negative terms. It's what they lack that defines them. But you have to remember that the terms eukaryote and prokaryote were never meant to have any evolutionary significance. They were meant to describe just the morphology of the cell. They were an organisational concept. And that's because appearances, even at a cellular level, can be deceptive.

• 7:34Speaker 06

  So, for example, hippos, rhinos and elephants, they all look similar. They're big, grey animals and they're grown in Africa. But they all descended separately from small furry ancestors.

• 7:46Speaker 04

  Different furry ancestors.

• 7:48Speaker 06

  Different furry ancestors, absolutely.

• 7:50Speaker 04

  Okay, so in the context of prokaryotes and eukaryotes, the complex cells, how did we understand that life had evolved before Woz made his discovery?

• 8:05Speaker 06

  So Buzz has already mentioned the limitations of the light microscope. And even going back to a Dutch draper named Anthony van Leeuwenhoek, he was the first person to invent the microscope. Because he was looking for threads and the quality of the cloth he'd been sold. And he scraped some gunk off his teeth and observed bacteria for the first time. And then we get the kind of light microscopes you'll be familiar with from school. But they're really not much good at doing anything other than seeing this cell is small and this one's big and this might have a nucleus in it. When we then get on to the electron microscope, now we can tell apart some of these internal structures. And one of the first things we notice is these mitochondria and chloroplasts actually look a lot like bacteria.

• 8:47Speaker 06

  And that then leads, and maybe we'll come back to this later, about the theory that Lynn Margolis put forward about how the first eukaryotic cells evolved by engulfing bacteria and domesticating them. But coming back to that ancestor that engulfed those bacteria, even if it was still around, even the electron microscope would have a problem turning it apart from other prokaryotes. Because at a microscopic level, all prokaryotes look like elephants, hippos, and rhinos.

• 9:17Speaker 04

  I see. So up until Rose's discovery, we just couldn't tell the difference between bacteria and archaea.

• 9:26Speaker 06

  Under the microscope, they look identical.

• 9:28Speaker 04

  So Krista Schleper, oh, you're looking a little skeptical there about that last statement. Maybe you can explain. So what was it that Carl Woese did to change all that, to change our fundamental understanding?

• 9:44Speaker 07

  So this is an interesting story. Carl Woese was really a pioneer. It was in the 1970s, and he was a professor in Urbana in Illinois, and he was a specialist for the ribosome. And the ribosome is a big machinery that every living cell has, and it is there for making the proteins in our cells. And Carl Woese decided that the genetic material of ribosomes could be used to find a natural history of the life forms, like what they are really related to, as Thorsten pointed out, the elephants and the other animals. And he decided that the genetic material of ribosomes would be perfectly suited because

• 10:24Speaker 07

  it's so conserved in all organisms, so that he could trace back evolutionary roots really, really far back. And he wanted to make a natural system of evolutionary relationships, stepping away from the morphological, you know, the shapes and all that, that was used to classify organisms. And he did this very early, long before DNA sequencing actually came into place in the late 1970s.

• 10:52Speaker 04

  Yes, so how did he do it if we didn't have DNA?

• 10:54Speaker 07

  It was hard work. It was hard work. He had to grow. The organisms with radioactive material and then he had to isolate the ribosomes and to find out about the RNA and then he chopped the RNA with different enzymes and then he got black spots on an X-ray film. And only from comparing these black spot patterns that he got, he could tell that he has found a third form of life, fundamental third form of life. Because there were certain odd bacteria, considered bacteria before, coming from odd places that showed a completely different pattern. As very different to eukaryotes, but as different also to bacteria. So it was clear it was a third life form.

• 11:35Speaker 04

  For listeners who are as troubled as me by this subject, we'll explain about the difference between DNA and RNA a little, a little later. But I want to carry on with what the implications of Woze's discovery was. So what does this imply for the origin of eukaryotes, complex cells like the ones in our bodies?

• 11:59Speaker 07

  So Cal Woos, he commented on this early on actually, that having three fundamental lineages of, of life forms. This will help us to understand at the end the, the evolution of eukaryotes. And so it cannot have been so easy maybe. That was also his idea. And so he relatively early on talked about the early split of bacteria and archaea in the evolution of life. So about four billion years ago, and that there was separate evolutionary lineages. But for him, it seemed more like a soup of events where you would have a lot of exchange of genetic material. And eventually he would think that there's a lineage, a little bit more related to archaea,

• 12:44Speaker 07

  which would have been the ancestor of an organism that later engulfed what Thorsten already mentioned, engulfed bacteria to form mitochondria and then later plasmas.

• 12:55Speaker 04

  So Buzz, following on from that, how do you picture this happening? I'm talking now about how archaea and bacteria started, how can I put it, hanging out with each other.

• 13:09Speaker 05

  I mean, this is one of the big mysteries in the history of life on Earth. In a way, it's one of the big problems in all of biology, up there with the seat of consciousness and the origins of life, because it was a step change. So, as we heard, for two billion years on Earth, there were simple cells, bacteria, and archaea, living together, often in communities, but nothing more, nothing bigger than something that you could see, you know, with a magnifying glass, something small like that. And then suddenly, we think it was suddenly, as oxygen rose in the atmosphere, these new creatures arose, and now we see them everywhere, in a walk in the woods, trees, you know, mushrooms, birds, so all this stuff is eucaryt, and as Torsten explained, the cells are profoundly different. So how do you do the jump?

• 13:50Speaker 05

  And so this has always been an area where, because there's nothing in between, there's simple, and then suddenly you have this jump to complex, how do you bridge the gap? And so there are lots of models out there, and people look at the thing through different lenses, but my journey into it was my cousin, David Baum, he answered a question when he was a student in university, where he disagreed with the textbook model, and he came up with this idea that maybe archaea grew into eucarytes from the inside out. So the idea is you have two partners, two cells living together in a sort of complicated

• 14:25Speaker 04

  So one bacteria, one-

• 14:26Speaker 05

  One bacteria, one archaea.

• 14:28Speaker 04

  Right.

• 14:28Speaker 05

  And then because archaea don't have a cell wall, they actually can have a flexible shape. So his idea was, which we then grew together, was that the protrusions can come out and enable two cells living together in an ecological niche to share resources and become more and more intimate with each other. And through growing intimacy, they kind of merge together over time to give rise to this common thing, which is the eucalyptic cell. But it would have been a long journey in the imagining, and there are lots of unknowns. And so Dave and I put forward this idea in 2014, but it was really just fantasy, speculation, and lots of other people had other models, but in a way, our timing was good.

• 15:11Speaker 04

  Well, you proved right, or don't we yet know?

• 15:14Speaker 05

  Well, the truth is, a model is only a model, we don't know and we're not sure whether we ever really will know because these events happened two billion years ago. But since that model, a group led by Tyse Etmer and your span with Christopher was involved in, really discovered this new creature that's really looks like a stepping stone between Simpulacan.

• 15:34Speaker 04

  We're going to come to that new creature a little later on, but before we do, the thesis that you and your cousin put forward was posited against the idea that Archaea had eaten bacteria. Is that correct?

• 15:49Speaker 05

  So I think the simple idea that one is that it's like a predation where a big cell ate a small cell and then couldn't digest it, that's sort of abrupt and it's sort of, it's dominance.

• 16:02Speaker 05

  So I think this idea is more like biofilms, which are everywhere on earth, where microbes live together, fighting and sharing, and these environments are everywhere and they're everywhere now on earth. And so it sort of frames it in that more ecological context where organisms start to share, become more intimate, and then do this amazing transition where suddenly two become one more complex, higher level individual, which is an amazing thing, which happened only once on life on earth, but it changed everything.

• 16:32Speaker 04

  Wow, and in order to forward that, I think you quote the theories of Prince Peter Kropotkin, who I know from reading about anarchism and its relationship to the state, but he had a whole different area of interest as well. What was Kropotkin saying about how life evolved?

• 16:54Speaker 05

  So there's always been these two threads in biology. There's the kind of selfish survivor of the fittest idea, which sort of came from Darwin. And there's always been this other idea, which Prince Kropotkin came up with, which is about the idea that when he went to Siberia, he realized organisms can only live together in some environments. So it's not just survivor of the fittest, organisms have to live together. And in fact, Lin Margulis, who's the one who Torsten mentioned, who showed that bacteria live inside. Of complex cells, she, you know, grew up in the sixties where again, there was an idea that we still live together in communes, so she looked at the cell and saw a commune where people were to love in together. And, and, and yet there's this selfish gene idea, which is sort of in opposition.

• 17:35Speaker 05

  So in a way, this transition of eukaryogenesis challenges it because we have two selfish cells fighting it out in a biofilm, coming together to give rise to a higher level consortium, which is this usually harmonious, not always collaborative venture, which is the complex cell, which our body is made of, and plants and all animals.

• 17:55Speaker 04

  Okay, to us then, back to DNA, transcription and translation and the role of RNA. Why are DNAs functions and RNA relevant to our story here?

• 18:10Speaker 06

  Perhaps the best way of illustrating this is imagine you working in a robotic car factory. The blueprints are stored on a computer. That's the DNA. They are then copied into a set of instructions. At a cellular level, that's done by an enzyme called RNA polymerase. RNA polymerase makes an RNA copy of the DNA. And that then becomes the set of instructions, which in our robotic car factory tells the robots what to do. At a cellular level, it tells the ribosomes which proteins to make. Now imagine that you're not actually looking at a robotic car factory. The factory's making other robots. And those robots go on to make other factories. And that's what the cell does. It wants to make more of itself.

• 18:53Speaker 06

  So going right back to the beginning, there's our DNA, the blueprint. It has to be copied every time we make a new factory. And that's done by another class of enzyme called DNA polymerase. It makes DNA copies of DNA. Now, when we look in the archaea, as opposed to bacteria, the enzymes that carry out these processes, so that's the DNA polymerase that copies DNA, RNA polymerase that makes an RNA copy, and the ribosome that then turns that RNA into protein. They are uncannily similar to the enzymes we find in us, in eukaryotes. And they are very different to the ones we find in bacteria.

• 19:31Speaker 04

  So this is the key thing about Archaea is is that they actually in some respects look like our cells. Is that right?

• 19:40Speaker 06

  Yes, they do.

• 19:42Speaker 04

  Buzz, you wanted to come in there.

• 19:43Speaker 05

  Yeah, and yeah. And so just following up on what it was instead. I mean, one of the wonderful things, in a way, the genius of Woz was he saw that because this machine, this ribosome, which contains RNA, is so well conserved across his life, it's the perfect system to test where do organisms come in the tree of life. And as you know, sort of mentioned, he saw that this machine, this really ancient machine, the one that we have is more related to the one in Archaea. So this is really the evidence that all the information processing that happens in our cells has its origins in Archaea. And that was really the clue that when you have a eukaryotic cell where the bacteria becomes a mitochondria, this energy production center, the rest of the cell, the information processing, really smells

• 20:28Speaker 05

  like it's Archaea, like Archaea.

• 20:33Speaker 01

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  This is Shirley Strawberry from the Steve Harvey Morning Show. Buy smart, drive for less, and trade for more. That's Toyota affordability. And it starts with a great deal on an all-wheel-drive Camry, Corolla Cross, or a Corolla Sedan with the latest features and tech. Or test drive a spacious Grand Highlander or adventure-ready RAV4. And with so many hybrid models available, you can enjoy longer trips without all the stops. While Toyota's legendary resale value means you could get more at trade-in, get a great deal today and a great value tomorrow. Shoptoyota.com for deals and details. Toyota, let's go.

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• 22:12Speaker 04

  Hello, Misha Glennie here. Did you know you can get episodes of In Our Time 28 days early with a subscription to the BBC website and app? Just head to bbc.com/subscribe to find out more.

• 22:29Speaker 04

  So Krista, you made a really important discovery when you were working on Archaea called Asgard Archaea. This was around 2015, I understand. How did the Asgard Archaea? Well, first of all, what are they? Where do they come from? And how did they change our understanding of the relationship between Archaea and eukaryotic structures?

• 22:53Speaker 07

  Yeah, everything changed, it feels like, in 2015. But before I come to the Asgard Archaea, I would like to point out what we already have known about Archaea before 2015. And that was that several people, actually in Europe mostly, who worked on the information processing system that Thorsten elaborated so well on how it works in a cell, that the information processing in Archaea has a lot of similarities to that in all eukaryotes, in all complex living beings. So this had been in place. And then in 2015, there was made like almost another step because we found organisms that have even more than those similarities.

• 23:34Speaker 07

  So a PhD student in my lab, I was professor in Norway back then, took samples from sediments near Loki's castle, which is the northernmost hot vent that has been discovered and was named after a Norwegian god, Loki.

• 23:49Speaker 04

  The god of mischief, I believe.

• 23:50Speaker 07

  Yes, yes. And these sediments were very interesting because they had very specific layers. They were very stratified, we say. And in certain distinct layers, we found a large amount of DNA, of genetic material, of archaea that we had never seen before in this amount and in this, you know, abundance. And so that was enough material to do genetic analysis. And this was actually done by Thais Etyma, Leonel Gueye and other colleagues, who looked into this genetic material from our student and found that the genomes can be assembled quite far and that these archaea have even more features that they share with

• 24:34Speaker 07

  the complex organisms than any other archaea ever had before. In fact, hundreds of genes were found that we had not seen in any prokaryote before. And so that was a big prediction. And on top of that, the phylogenetic analysis, or the phylogenetic trees they built to find out the relationships showed that these, what are now called Asgard archaea, actually are the closest lineage to eukaryotic organisms. So actually, that as if complex life came like from this archaeological branch, directly from there.

• 25:08Speaker 04

  So let me get this straight. This is as close as we've got to finding out the origin of complex eukaryotic cells?

• 25:17Speaker 07

  Yes, that's what we think now. And they actually look a little bit different in the microscope. That was the next step. We have to come to that. That's why I had this little comment before, because they look slightly different already. So there is a lot of transition going on in that lineage indeed. But first, I would like to tell that they are also very diverse. From 2015 on, there were a lot of more lineages found that are all related to these Loki archaea and that are now called Ingyn and Heimdall and Thor, all these Norwegian gods. Also, one Chinese god, Wukong, but mostly Nordic gods. And that's why they are collectively called the Asgard, because in the mythology, that is the home of the Nordic gods, right?

• 26:00Speaker 04

  Well, that's a sort of divine relationship, but Buzz, there's also a tendency to anthropomorphize archaea. What do they look like? How do they move? What do they do?

• 26:11Speaker 05

  Well, maybe just building on what Krista said, I mean, one of the, so there really was a revolution in two thousand and fifteen when this, these genomes were put together. You know, it was a revolution that had all these things that make them look like, have genes that resemble things that we have. The question is, what do they look like, the cells, like, and how do they behave? And we had to wait and wait and wait, and I wanted to know to test our model, but lots of people wanted to know. And in two thousand and twenty, we got our first glimpse from a study by Imachi and Nobu, who'd spent twelve years cultivating creatures from the bottom of the sea off the coast of Japan in anaerobic conditions, without oxygen. It was incredibly hard work, and in their images, they saw these extraordinary cells

• 26:54Speaker 05

  with long protrusions, which only live with other organisms in partnership. So in a way, this really did look like something that completely new way of seeing archaea. They look completely different to any archaea, and they lived in communities. And then there was this amazing thing that Krista's team then followed up with beautiful studies using electron microscopy, where they cultivated their own one from Slovenia, the bottom of a lake. I mean, Krista should speak about this more than me, but the images were gorgeous. With electron microscopy, we could see that not only did these cells have like information processing machinery like us, but they have the kind of underlying cellular structure

• 27:36Speaker 05

  that resembles, for example, a migrating dendritic cell in your body that's hunting down bacteria, like one of our cells. And recently Krista's team has really shown that they do stuff in culture which looks a bit like one of our cells. So suddenly, this huge gulf between complex and simple life has been bridged by this mischievous, low-key, Ascot archaea.

• 27:57Speaker 07

  One could call them the Archaeopteryx lineage, because it is like a transition, right? Like the flying dinosaurs, you know, that have died out, but that are the transition from dinosaurs to birds. This is here, you could do that, like a missing link, one could call it, between the prokaryotes and the eukaryotes, kind of.

• 28:15Speaker 04

  This is extraordinary. Torsten, tell me about how archaea

• 28:21Speaker 04

  Manage to survive in these extreme conditions where we can't. Um, ludicrous temperatures like ninety degrees centigrade, as Buzz mentioned, and very salty environments. How do they do that?

• 28:34Speaker 06

  Well, actually, in excess of ninety five degrees, at the bottom of the ocean, at some of these hydrothermal vents, because you have so much pressure of all that water above you, you can get organisms growing at a hundred and ten degrees because the water won't boil down there. How do they manage it? It's surprising. When you look at the proteins in these Archaea that grow in these conditions, they're called thermophiles because they love heat. They look remarkably like us. And this is surprising because if you take an egg and put it in a hundred and five degree centigrade water, all the proteins in the egg white, they unravel and coagulate. And it makes a really nice breakfast for us,

• 29:17Speaker 06

  but it's not much good making a new chicken. So you would think that that would be a problem for Archaea, but they solve this by having the same structure of our proteins. But they have lots of internal bridges and buttressing that makes them much stronger on the inside and much less likely to unravel at high temperatures. But there is a downside to this. If you now take one of these Archaea proteins and you bring it down to our temperature, they become too rigid. They can't do stuff anymore. Now, you would have exactly that same problem if, let's say, you're still driving an internal combustion engine car, and you now want to take it to the Sahara. Your mechanic is going to tell you, you need a thicker grade of oil

• 30:00Speaker 06

  because your oil is going to be too runny in the Sahara and your engine's going to wear out. If you take that same car now to the Antarctic, it will seize up because the oil's too viscous. And it's the same thing at a microscopic level with the proteins in the thermophiles.

• 30:13Speaker 04

  Um, this may sound like a tangential question, but why are flamingos pink?

• 30:20Speaker 06

  So this goes to a subject very dear to my heart, which are halophiles. These are organisms, archaea, that thrive in very high salt conditions. So high salt is, imagine you've put too much soy sauce on your Chinese meal. That's how salty, and worse. So the Dead Sea, as Buzz already mentioned, this is where we find them. Saltworks, and if you've ever been to a saltworks or to any of these seas in Australia, they have some great examples of salt lakes there that are bright pink. The bright pink coloration, that's in the membranes of these halophilic archaea. And they form food for some microscopic eukaryotic organisms, brine shrimp, which feed on them.

• 31:05Speaker 06

  And in turn, the brine shrimp are food for flamingos where we find them. So if we didn't have the red coloration in the halophilic archaea, we wouldn't have pink flamingos.

• 31:16Speaker 05

  And it's also why if you buy Himalayan salt, it's pink, because, partly because of the archaea.

• 31:22Speaker 04

  So we're eating archaea when we eat Himalayan salt. Krista, where do we see the impact of archaea in the ecology, in the environment, in the ground, in the atmosphere, in water?

• 31:34Speaker 07

  Yeah, so this is also important to mention because archaea are very interesting for their adaptations and evolutionary aspect, but there's also a big aspect of ecological effects on Earth. And the one group is the methanogenic archaea. These were the ones that Carl was first investigated, by the way, when he found out about the relationships. And methanogenic archaea are almost everywhere, but they don't like oxygen. So they are in all anoxic environments, in the marine sediments, in a lake, down in a lake bottom, they're also in our gut system, right, where it is, where there is no oxygen in some places. And these methanogens are important for ecosystems because they are at the end of the food chain.

• 32:16Speaker 07

  They use the very last products from bacterial and fungal degradation and convert it into methane, which is again a food for other bacteria when it bubbles up, you know, it's a gas, and then it comes up. And it's the food again for bacteria to degrade it further on. So it is an important part in the, we say, global bio-geochemical carbon cycle. But it is also problematic because with global warming, methanogens in the Arctic soils, where the permafrost is thawing, or methanogens in wetlands around the equatorial area, they are producing more methane now, they become more active. And methane is a very strong greenhouse gas, and it is responsible for the debates,

• 33:00Speaker 07

  but 25 to 30% of global warming effects, because it's a very strong greenhouse gas, 30 times stronger than CO2. So that is one group, that is important to look at. They also have a lot of good sides. You can also make biogas from them, which is also the same thing. But, uh, yeah, one has to keep an eye on them, one could say. And the other group is ammonia oxidizing archaea that occur, or that are found in many soils and in the ocean and virtually everywhere where you also have oxygen. So they also occur, they also live on our skin, actually. We have just isolated an organism from our skin, but they are good, they are good for our skin, we think. We have not proven that.

• 33:42Speaker 07

  But these organisms are involved in the global nitrogen cycle, which has to do with fertilization, how we produce food. You know, and fertilizer is escaping into the surface waters, and part of this problem can be traced back to archaea that feed on these nitrogen compounds or to also certain bacteria groups.

• 34:02Speaker 04

  And can any of you chip in on cattle, methane and archaea?

• 34:07Speaker 06

  I can. This is, so Chris already mentioned where methanogens, these are archaea that produce methane, they live in our gut. They don't just live in our gut, they also live in the guts of cattle. And we have a much bigger consequence when we look at cattle metabolism. So what are they doing in there in the first place? So Chris already mentioned that they feed off the end products of bacterial fermentation of products that we cannot digest. So it's principally dietary fibre that we cannot digest directly, that bacteria then ferment. The end products of their fermentation, hydrogen and carbon dioxide, are turned by these methanogenic archaea into methane. And we emit about 350 millilitres of methane every day.

• 34:52Speaker 06

  But that pales into insignificance compared to cows, which put out about 200 litres of methane a day. And given that methane is 20 times more potent than carbon dioxide, we now have a big problem on our hands.

• 35:04Speaker 04

  Talking about food cycles, what's the favourite food of some of the archaea you study?

• 35:11Speaker 06

  I think we all have to chip in here. Let me start then with halophiles that we grow in my laboratory. These have a very simple diet in microbiological terms. Because if you're a microbiologist and you don't know what to feed something, you feed it powdered marmite, yeast extract. Nearly everything grows on this, nearly everything. They then have some additional requirements on top of that.

• 35:38Speaker 05

  Well, the thing, but the thing in a way, though, is that because these microbes live in communities, and as we heard from Ascards, they'll live with, they have to live with other cells to actually survive. You know, you could have two cells living together where one likes the marmite, the other doesn't, but that one can use the marmite and release its waste products, which the other one can then use in turn. So this is the sort of principle of symbiosis, which archaea and all microbes, in fact, engage in all the time. So our idea about, you know, individual organisms living by themselves, fighting each other, is wrong in that sense, that food can be shared by different organisms.

• 36:10Speaker 04

  I have got to say, I can't help notice the tremendous enthusiasm that researchers working with archaea, the enthusiasm they express, but these things are very hard to study. I mean, if you've got something living at ninety five degrees or more, how do you get them back into the lab and look at them?

• 36:30Speaker 05

  It's incredibly hard. And in order to work on them properly, my lab had to ditch everything else we're working on, flies and human cells, and to work on archaea, because each one requires devotion. You have to really love them to get them to grow, some more than others. But the thing is, it's so rewarding because they haven't been studied, we don't know how to grow them, it means that when you discover things with them, they're completely new. But my lab, for example, in the last few years, spent five years trying to build a microscope that will work at seventy five degrees centigrade, which if you touch it, you burn your hand, which is ambient for these organisms from Yellowstone National Park that grow in these sort of sulfurous volcanic springs. And then we had to evolve proteins

• 37:15Speaker 05

  we can put inside that emit light, so we can see how proteins move in these things. So these things were for a bacterial cell or human cell are, were done decades ago. But archaea, if you want to do anything at all, you have to invest huge amounts of time learning to nurture them, love them, and then find ways to engineer solutions so you can actually study them.

• 37:35Speaker 04

  Did you succeed in inventing the seventy five degrees?

• 37:38Speaker 05

  Yes, and it's, and it's, the trick is to heat the lid.

• 37:42Speaker 04

  Congratulations. Krista, Buzz has told us about how you look at them in the laboratory, but how do you go and get them in the first place if they're in Lochie's Castle down at the bottom of the sea? How on earth do you find them?

• 37:56Speaker 07

  Good point, good point. So, so to get them from Lochie's Castle is of course with a submarine, you know, with an ROV, they have been taken. But those are also difficult to work with, and we have not succeeded yet to culture them from Lochie's Castle. But we are, we are using marine shallow marine sediments, and there also we take care that we keep them without oxygen. So we bring them in a little tube. We bring them home to the lab, right there at the site where we take them and then we inoculate, we put them into new flasks and try to grow them right away and try to avoid oxygen right away. That's one thing. But then there's also other archaea, for example. I have also many years ago isolated one of the most acidophiles, which means an acid lover.

• 38:41Speaker 07

  So if you isolate an acid-loving archaeon, you need to be very careful how to bring it home because it will be killed because it needs its own activity and metabolism to be able to cope with the acid. And so you have to shift a little bit, where you have to dilute out the acid a little bit, but not kill it because it needs acid also. So you need to find compromises. And there's an interesting story from the 1980s, when the first archaea were discovered as such from Calvus, then people went out like, people like Wolfgang Zillig, who were strong proponents of Calvus's idea because of their findings. And they went out to get novel organisms from hot springs and they brought a thermal bottle, you know, at the beginning because they thought you have to keep them warm.

• 39:25Speaker 07

  You have to keep them like they are in the warm water, but that was not true. They're actually happy to get cooled down because then they become more inactive. Then they are like, like we would be frozen, kind of. So it depends.

• 39:38Speaker 06

  So I have to say that not all archaea are that difficult to work on. So traditionally, if you have wanted to work with the organism in the laboratory and do some more complicated genetic experiments and not spend all of your time and energy like Krista and Schleper and Buzz here, trying to keep them alive, you work with halophiles. What do you need besides marmite? You just need a lot of salt. Pour in salt until it becomes almost saturated. And actually, conversely, if you want to decontaminate something, if you accidentally spill some of these halophyle archaea on the bench, wipe it down with water. It kills them.

• 40:15Speaker 07

  Yeah, but you have other problems with your halophiles because it's very hard to do biochemistry, for example.

• 40:21Speaker 06

  Well, it is.

• 40:22Speaker 05

  And electron microscopy is very hard with halophiles.

• 40:24Speaker 06

  Okay, so there's no perfect species. Yeah. So it turns out that what Krista is referring to is that the way that halophiles cope with high salt is they have salt inside the cells as well as outside. And it means that all of their enzymes have to be able to function in very high salt concentrations, which brings with it its own challenges, including for us if we want to study those proteins in the laboratory using biochemistry. So I avoid doing biochemistry.

• 40:53Speaker 04

  You mentioned a little earlier on about the fact that they live in our gut in an anaerobic environment. Now, this is, I'm going to confess my huge ignorance here. I didn't realise things could live without oxygen, but most of these archaea apparently seem to thrive outside of an oxygenated environment. Why is that?

• 41:14Speaker 06

  The answer to that is partly because the enzymes they use to make methane are poisoned by oxygen. So they have to grow without oxygen. You only find them in environments like our gut, like landfall sites, like swamps, where, in fact, the first person to ever discover methanogens was Alessandro Volta, back in the 18th century, from whom we also have the term Volt. And he was poking around in some swamps in northern Italy and noticed some bubbles of methane coming up, and arguably he's the first person to have discovered methanogens.

• 41:49Speaker 05

  Because they caught fire, right?

• 41:50Speaker 06

  They caught fire, yes. You can light fire to methane.

• 41:54Speaker 04

  Buzz, you were going to come in there.

• 41:56Speaker 05

  Yeah, I mean, also, we have to remember that, you know, we call archaea extremophiles, but of course, they think we're extremophiles. And one reason, for example, to make that distinction is for most of Earth's history, there was no oxygen in the atmosphere. And so for 2 billion years, archaea and bacteria were living on a planet with no oxygen. And in fact, the increase in oxygen about 2.5 billion years ago, made by cyanobacteria doing photosynthesis, changed everything, led to a catastrophe in a way that lots of things that couldn't live with oxygen suddenly died. And archaea had to hide away in these places which are still anoxic, like in our guts and in sediment. But this also meant that at the margins, you could have new evolution, new things like complex cells.

• 42:39Speaker 04

  So, Krista, did complex cells come because oxygen suddenly appeared?

• 42:46Speaker 07

  Yes, this is, this is probably the case, yeah. This is probably the case. So, so the idea at the moment, there's a little bit of a debate, what the Asgard Archaea, the exact Asgard Archaea that maybe we are looking for, that were existent two billion years ago, we cannot find them nowadays, of course, but something similar. If they were, how much they were already adapted to the first oxygen and how much they actually then profited from engulfing a bacterium that was already coping with oxygen. And because why did life expand so much with oxygen, also the new forms of life that could cope with this, is because you can gain a lot of energy when you have oxygen involved, right, when you can breathe oxygen and not other chemicals.

• 43:30Speaker 05

  Which is why we burn, we burn hydrocarbons in oxygen, you know, to drive planes and cars for that reason, generates a lot of energy.

• 43:38Speaker 04

  Let's have a final question. Bacteria, we have good bacteria and we have some very bad bacteria. Do we have good archaea and bad in terms of their relationship with us, pathogens that cause disease?

• 43:53Speaker 06

  So, we have archaea that grow inside us in our gut, as we've already mentioned. And it's a big mystery in the field, why none of these become pathogenic, cause us any disease, because we have bacteria that grow in our gut, which if they can then overtake the good bacteria, cause us all kinds of gut problems. This doesn't seem to be the case with archaea. Now, why might that be? One thing that we've not touched on so far is that archaea have on the outside of the cell, a fundamentally different membrane structure to the one that we have and that bacteria do. And that different membrane structure both gives them extra thermo stability, allows them to colonize high temperature environments.

• 44:37Speaker 06

  But it might also make them a really good target for our immune system. Buzz?

• 44:42Speaker 05

  Yeah, I mean, the thing is, Thorsten said also, I'm not sure we know the consequences of our care for our health. We know we've been living them for a long time because when they looked at the DNA on the teeth of Neanderthal skeletons, they found the same archaea that we have in our teeth. So our ancestors are not just making babies together, also kissing and sharing food maybe. But it means they've been living with us a long time. They're in our guts. When we take antibiotics, it kills the bacteria, not the archaea. But when you take statins, actually, it kills the archaea. And there are no studies, like, we don't know yet, I think, the consequences. So it's true that archaea, there are no diseases we know about. And they do grow slowly as well, and they might be seen by the immune system. But I think, watch this space, who knows how important they might be for our health and...

• 45:25Speaker 06

  But actually, on that point, just very briefly, Buzz, you can take statins to cure constipation due to excess methanogenic archaea.

• 45:33Speaker 04

  Well, well, well, my huge thanks to Krista Schleper, Buzz Baum and Thorsten Allers. Next week, it's Dadaism, the nonsensical chaos that emerged in the Zurich art world during the First World War. Thanks for listening.

• 45:47Speaker 02

  And the In Our Time podcast gets some extra time now with a few minutes of bonus material from Misha and his guests.

• 45:56Speaker 04

  Well, and now we can go over to the podcast thing. I have to tell you, I, I'm going to be honest here. I had no idea. I didn't even know archaea existed. And as I was doing the research for the programme, my jaw just dropped further and further down. It's absolutely fascinating.

• 46:20Speaker 06

  But you're not alone. Most scientists don't know they exist either.

• 46:23Speaker 05

  And they can't pronounce archaea either. Most of my colleagues don't know.

• 46:27Speaker 07

  Maybe the problem is actually the name, that is, that they are not so famous. I don't know.

• 46:32Speaker 04

  Yeah, yes and no, I don't know.

• 46:34Speaker 07

  It's a good name, okay.

• 46:35Speaker 04

  So what else have we, what else have we, we missed out? I mean, I think the key thing for me and what I was trying to understand is that relationship between our cell structure and their cell structures, or at least what we, what we share in common with them. Do we have a similar relationship to bacteria?

• 46:58Speaker 04

  Well, help me, please.

• 47:00Speaker 06

  So it depends on your perspective.

• 47:04Speaker 05

  That's true.

• 47:05Speaker 06

  Right, so from my.

• 47:06Speaker 05

  I have a stop.

• 47:07Speaker 06

  Okay.

• 47:08Speaker 04

  You start.

• 47:09Speaker 06

  All right. My, my perspective here is that I work on DNA replication. So how we turn one molecule of DNA into two molecules of DNA. Why do we even have this two step process of turning DNA into RNA and then RNA into proteins? Because DNA is more stable. But if you wind back the clock, we all now think RNA was the original genetic material. So it must have been an RNA polymerase that made new copies of RNA.

• 47:36Speaker 04

  So it preceded DNA.

• 47:38Speaker 06

  It did, because RNA, as well as being able to code for itself, can do catalysis, something that DNA can't do. It's just down to a single oxygen atom. This is where we have deoxy.

• 47:51Speaker 04

  Just explain catalysis for us.

• 47:54Speaker 06

  So catalysis is, you can have non enzymatic catalysis. That's chemical catalysis.

• 48:00Speaker 05

  It means speeding up a reaction. So something that won't go.

• 48:02Speaker 04

  As in catalytic.

• 48:03Speaker 05

  So for example, a piece of wood won't burn.

• 48:05Speaker 06

  Yep.

• 48:05Speaker 05

  Because it just sits there. But if you add a catalyst, like you, like you heat it up, it's suddenly you get a flame.

• 48:10Speaker 06

  Yeah.

• 48:11Speaker 05

  So it, yeah.

• 48:11Speaker 06

  Yeah, so for example, the platinum in your cast catalytic converter, that's a chemical catalyst. But you can also have an enzymatic catalyst, so it'll speed up a biochemical reaction. RNA can do that because it's got an oxygen atom on its backbone that's very reactive. DNA is lacking this. So it can't do catalysis, but that, on the other hand, makes it much more stable. And that's where we have this now split of things. But when it comes to archaea and the enzymes that make new copies of DNA and new copies of RNA, there's a really fascinating discovery that came out about six, seven years ago. The DNA polymerase that makes new copies of DNA,

• 48:56Speaker 06

  there's a version of this enzyme that we find in archaea, and only in archaea. And at its core, the bit that does all the work, looks like a dead ringer for RNA polymerase. So if we trace the clock back to the beginning of life, RNA was there first, being copied by RNA polymerase. When we now make that leap to DNA polymerase, perhaps this is still the DNA polymerase that did that first bit of DNA copying. And we only find it in archaea. We find bits and pieces of this DNA polymerase now in us, in eukaryotes, but it's since been supplanted by other more efficient enzymes.

• 49:38Speaker 07

  But when it comes to quantity of genes or enzymes that we share with eukaryotes, or with archaea, that us eukaryotes share with archaea, then it is not so many. It is because you think, Thorsten, and I agree, that information processing, these events, are maybe the most important in a cell. But if you argue from a metabolic point of view, how we gain energy, or things like this, then actually, there is a lot from the bacteria in us.

• 50:05Speaker 04

  So mitochondria, for example. Can we explain about mitochondria? Because it was introduced as a concept, but not everyone.

• 50:14Speaker 05

  Yeah, so the complex cells, eukaryotic cells, have these two, we think, at least contributing organisms, an archaeal cell and a bacterial cell. And the bacterial cell is the one that then does, acts a bit like a bacterial cell, in living in oxygen. It will burn hydrocarbon oxygen to generate energy, which then it gives to the whole. And the rest of the cell, a lot of the machinery, as we said, comes from the archaeal side. Now, you can look at the two and sort of look at it like an equal partnership, but the truth is, when you look at a eukaryotic cell, one of our cells, down the microscope, there is a bacterial-like mitochondrial sitting there, which is why Lynn Margulis said, there's a bacterial cell living inside, and other people had seen that before for chloroplast. It really looks like a bacterial cell.

• 50:59Speaker 05

  The archaea, the rest of the cell looks completely alien, like this, you know, where did it come from? Woes didn't think it came from, you know, thought it has a sort of a separate lineage. But now, we know that there are archaea, which as Krista sort of said, have many of the things that we thought had never been seen before in any procarate. So for example, we, my lab, we would argue, we've now seen even compartments with inside archaea. They have long protrusions, they move, Krista's lab has shown they can move, but also the information that they contain is, is, is in case sort of in a hub at the middle. And they have these long protrusions, which are a bit like the edge. So very much like our cells, we think they have spatial separation between information

• 51:40Speaker 05

  storage and execution. So what archaea do is they change the way you look at cells. Because before the discovery of ascolicae, you couldn't really see the origin. But now we're learning to look afresh at these archaeal cells and see in them, maybe a proto-nucleus, maybe a proto-cytoplasma, maybe, you know, cell motility, maybe compartments that resemble the compartments we have in our cells. So suddenly, they, these ascol really are like a stepping stone from simple to complex that give us clues about how it worked. But of course, the eukaryotic cell really requires the mitochondria. So you might have a very complex archaeal ancestor, but until the mitochondria came on board, it wasn't this amazing thing that can make a bird of paradise and a mushroom.

• 52:24Speaker 06

  Right.

• 52:24Speaker 07

  And we should maybe also refer to the other studies that, that argue maybe there were more partners, because there's more bacterial type genes in our cells that might have come earlier. There is a way of doing that, just transferring one gene by the other, not by such a big merger, but by individual processes. And this has also been hypothesized.

• 52:44Speaker 06

  Right. So the archaea, sorry, are very, much like a blended family. And we inherit not just genetic components by vertical lineage, the way that we like to think of a family tree, but also we acquire them laterally, by genes which have been traded between cells and sometimes hitchhiking on viruses.

• 53:06Speaker 04

  So they speed up evolution, that's me.

• 53:08Speaker 05

  I mean, this in a way was one of Woze's, again, one of his brilliant insights is that if you look at actually all organisms on earth back to in our care, actually genes move all the time. They'll, and that's why people in hospitals get these, you know, antibiotic resistance, because these, these bits of DNA jump. But Woze realized that the one thing that doesn't jump is this core information stuff. And that is inherited as cells grow and divide in two, and their daughters grow and divide in two. So in a way, although there's been all this mixing of genes, there's a one cell lineage on earth. There was one cell and we are all its progeny. And it gave rise to two branches, our can bacteria, and each of those cells grew and divided into a single lineage, which then fused to give rise to you carrots.

• 53:48Speaker 07

  Two billion years later.

• 53:49Speaker 05

  Two billion years later.

• 53:49Speaker 07

  Wonderful story, actually, it goes like this.

• 53:51Speaker 04

  Good, good God. So, so Krista, so we have three branches, also known as three kingdoms. You're, you mentioned a researcher who you worked with, Volfran, Volfran Cilic. Why was he so distressed about the three kingdoms?

• 54:09Speaker 07

  Yeah, this was at the time when

• 54:12Speaker 05

  Not just him.

• 54:13Speaker 07

  Not just him, maybe. That was at the time when, when these kingdoms were also called Reich, Reich in, or so Urreich even, you know.

• 54:24Speaker 04

  So Reich meaning empire in German, of course.

• 54:27Speaker 07

  Yeah, also exactly. And then when he heard about it, there was this researcher in Illinois who had found a third Reich of organisms. He was not pleased, you know, it was in the nineteen seventies, eighties.

• 54:41Speaker 04

  And he was a committed anti Hitlerite.

• 54:44Speaker 07

  Yes, he was very committed.

• 54:47Speaker 04

  So that's a rather unfortunate name, the Third Reich, particularly as it's describing something that is just so dramatically wonderful.

• 54:54Speaker 07

  Yeah, but now we talk about domains, so that has

• 54:56Speaker 04

  So we're back, good, domains, the third domain. That's good. Um, I, it's almost time for, almost time for a cup of tea, but I, you know, I mean, I've, in the short space of time, I have learnt so much. About which I I I knew nothing. This has been a fantastic discussion and thank you very much for everything. Buzz, do come in there.

• 55:21Speaker 05

  I just want to say, one thing I just wanted to say maybe that I think is so exciting about RKL research is because it it almost changes the way. So everything you learn in a textbook, when you start working RKL, it all falls away. But it also means that you start to realise, like, it's not Survivor of the Fittest. Things can live together. They can also, they affect ecology. So you have to look at cells in light of evolution, ecology within the world. So for me, it is like, also, RKL researchers are the ones who are studying life in the environment in an evolutionary context, which is, as Woz would say, I think, proper biology.

• 55:54Speaker 04

  Simon.

• 55:55Speaker 05

  Who'd like tea and who'd like coffee?

• 55:57Speaker 04

  Tea, please.

• 55:58Speaker 06

  Tea, please.

• 55:59Speaker 05

  Tea. Four teas. Thank you very much indeed.

• 56:02Speaker 06

  Thank you very much.

• 56:03Speaker 04

  Thank you.

• 56:05Speaker 02

  In Our Time with Misha Glenny is produced by Simon Tillotson and it's a BBC Studios production.

• 56:11Speaker 01

  Hi, we're the Van Tullikens, the identical twin Doctor Van Tullikens, Chris and Zand. In What's Up Docs, we're diving into the messy, complicated world of health and wellbeing. We are living in the middle of what I would call a therapeutic revolution, but it can sometimes be hard to know what's really best for us. Do I need to take a testosterone supplement? How can I fix my creaky knees? Why do I get hangry? Is organic food actually better for me? We're going to be your guides through the confusion. We'll talk to experts in the field and argue about what we've learned and share what we've learned.

• 56:43Speaker 03

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• 56:44Speaker 01

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• 56:46Speaker 03

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• 56:54Speaker 04

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