In Our Time - Microbiology

Episode Date: March 8, 2007

Melvyn Bragg and guests discuss the history of microbiology. We have more microbes in our bodies than we have human cells. We fear them as the cause of disease, yet are reliant on them for processes as diverse as water purification, pharmaceuticals, bread-making and brewing. In the future, we may look to them to save the planet from environmental hazards as scientists exploit their ability to clean up pollution. For microbes are the great recyclers on the earth, processing everything – plants, animals and us. Without microbes life would grind to a halt. How did we first discover these invisible masters of the universe? The development of microscopes in the 17th Century played a key part, but for a while science seemed stuck in this purely observational role. It is only when Louis Pasteur and Robert Koch began to manipulate microbes in the lab two hundred years later that stunning advances were made. These breakthroughs led to an understanding of how microbes transform matter, spread disease and also prevent it with the development of antibiotics and vaccines.With John Dupré, Professor of Philosophy of Science at Exeter University; Anne Glover, Professor of Molecular and Cell Biology at Aberdeen University; and Andrew Mendelsohn, Senior Lecturer in the History of Science and Medicine at Imperial College, University of London

This BBC podcast is supported by ads outside the UK. Thanks for downloading the In Our Time podcast. For more details about In Our Time and for our terms of use, please go to BBC.co.com.uk forward slash radio 4. I hope you enjoy the program. Hello, today we'll be talking about the history of microbiology. We have more microbes in our bodies than we have human cells. We fear them as the cause of disease, yet are reliant on them,

for processes as diverse as water purification, pharmaceuticals, breadmaking, and brewing. In the future, we may look to them to save the planet from environmental hazards as scientists exploit their ability to clean up pollution. For microbes are the great recyclers on the earth, processing everything, plants, animals and us. Without microbes, life would silt to a halt. How did we first discover these invisible masters of the universe? The development of microscopes in the 17th century played a key part, but for a while science seemed stuck in this purely observational role. It's only when Louis Pasteur and Robert Koch

begin to manipulate microbes in the lab 200 years later that stunning advances were made. These breakthroughs led to an understanding of how microbes transform matter, spread disease and also prevent it with the development of antibiotics and vaccines. So what do we know about how microbes operate? How can they contribute to environmental stability? And how to advances in genetics in microbiology help our treatment of diseases like cancer? Here to discuss the history of microbiology are Anne Glover, Chief Scientific Advisor for Scotland

and Professor of Molecular and Cell Biology at Aberdeen University Andrew Mendelsohn, Senior Lecturer in the History of Science and Medicine at Imperial College University of London and John Dupre, Professor of Philosophy of Science and Director of Eugenius at Exeter University. John Dupre, how would you define the microbe?

Well, that's not an easy question to answer because microbes are enormously diverse. Most microbes are single-celled organisms, but that is a hugely diverse. category. Currently we divide life into three main categories and two of those are what we used to call bacteria. Now we say bacteria and archaea and all of those are microbes. Then the third category or domain of living things we call eukaria and includes things like ourselves, animals, plants, but also all kinds of microbes, so protozoa, yeast, most of the fungi. So there's an enormously

diverse. These latter sort have a more. complex cell structure. But on top of these, there's also about 10 times as many of all of these put together viruses, which many people will count as microbes. So really almost all living things are microbes, and most of the diversity of life is within the category of microbes. So it's not an easy category to define. So there's no satisfactorily, for people like me, single and simple definition of a microbe. I think that, unfortunately, is the truth, yes. Well, we're liberty. Why are microbes so important? Well, I suppose one way of looking at it is that we've tended to look at life very much

from the perspective of seeing ourselves as typical organisms. And actually, we're very untypical organisms. And it's rather like we're looking at tips of icebergs floating around, which are, you know, animals, trees and things. But most of life is going on out of sight beneath waterline. I mean, if you look at a forest, you, you see, think of these trees, perhaps of separate things. If you looked underground and looked at the way their roots were interconnected with communities of fungi and bacteria, you'd find that were actually joined up in very intimate ways,

that they were actually part of a system that was interconnected. If you look at us, as you mentioned at the outset, most of the cells, 90% of the cells in our bodies, are microbes, and we tend to think of the human genome as defining who we are. But actually, that's a very small part of our genetics even. So, and Glover, just to give people some idea of numbers, I mean, what sort of numbers of microbes in a human being or in a tree compared with other cells?

Well, in terms of the human, I mean, there's trillions and trillions of microbial cells in our body. They're all over every surface of our body. They colonise our gut. They're in our hair. They're on our face. I mean, they're everywhere. We're like a walking microbial community. What role did microbes play at the beginning of life on planet?

planet Earth? Well, an extremely important role. If we think about planet Earth formed about 4.6 billion years ago. And at that time, the external environment would have been incredibly extreme. There would have been hardly any oxygen. There would have been an awful lot of sulfur gas. It would have been carbon dioxide, some methane, some hydrogen. But none of the conditions that would support life, as we understand it today. About a billion years after that, So about 3.8 billion years ago. We saw the first, initially there was chemical evolution, and then we saw the first biological evolution.

And there were bacteria and archaea, very simple forms of I say simple, but read that simple in inverted comments because there's nothing simple about them really. But these small single-celled organisms evolved. And they continued to evolve for about a further billion years until a very remarkable thing happened and quite a crucial thing for life.

and diversity of life. And that was a group of bacteria called the cyanobacteria. And if you look at them down a microscope, what they're like is like a miniature version of a plant. And what they do is they harness sunlight and they take the carbon dioxide, which would have been fairly abundant in the atmosphere, and they incorporate that carbon dioxide into biomass.

And a byproduct of that reaction is the evolution of oxygen. So what then happened was that our atmosphere went from less than, say, 0.1% oxygen concentration to roughly what we see now, which is about 21% or so oxygen. And those conditions then favoured the massive explosion of different types of life. Before we turn to the history of the development of the study of microbiology, I'd just like to ask you most people listening will think that microbes cause disease. and yet we seem to co-exist quite happily in our bodies alone, with trillions of the things.

Are there disease-carrying microbes and benign microbes? Is there a differentiation there? Or can all microbes switch from one to the other? Generally, there are a group of organisms, a microorganisms which would cause disease, and the vast majority do not and cannot cause disease under any circumstance. In fact, they're positively beneficial

to us. There is a very small group of organisms which can opportunistically cause disease so that from our point of view a healthy individual wouldn't suffer from disease when infected by some of these organisms but if you were immunocompromised or unhealthy in some way then you might be susceptible but generally a tiny tiny fraction of microbes would cause disease. Thank you very much. Andrew Mendelsohn. Let's turn to the history an hour. I think it's quite useful, but you'll tell me if it isn't, to start in the 17th century

with the development of the microscope. And can we concentrate on two figures, Robert Hook, and Lewin Hook, Englishman and a Dutchman, what they found to the microscopes and how that could be said to have kicked this whole study off? Right. I think it is useful, but possibly not for the reasons that you might imagine. I mean, the word microbiology contains in it a reference to the microscopic scale of the science. And yet, I would say, that microscopy did not really drive the creation of microbiology. Now, this is not to belittle the achievements of people like Lavinhook, a Dutch draper, who did study the natural world on the side,

and Robert Hook, who was an English natural philosopher instrument maker in London in the 17th century. Now, Levenhook was working with a microscope that is a tiny contraption that can fit, in the palm of your hand, and when I pass a replica around in class, the students can't find the lens because it's a little tiny bubble of glass sort of hidden in the brass workings of this thing. Hook was working with the cyclotron of its day, which was a large, expensive instrument owned by the Royal Society, where he was the curator of the instruments. He couldn't have owned it himself, and it was sort of one-of-a-kind thing. And Leavenhook would use his microscope to look at all sorts of various things. And I suppose what people think of when they think of Levin Hook

and microbiology is the letters that he sent to the Royal Society reporting tiny animals, as he called them, that he found in raindrops. And when people think of Hook, they think probably above all, well, certainly they think of his book, Micrographia of 1665, which is one of these large, wonderfully illustrated early scientific volumes that has a particularly famous plate, an illustration of the microscopic structure of various plant substances, which looks rather honeycomb-like, which he described using the word cell. However, there's no relationship, or almost no relationship, but between cell as he saw it and cell as it came to have a biological meaning in the 19th century. Now, if microscopy were absolutely the fundamental

driving force in the creation of microbiology, then we expect to see a couple of things. Number one, we'd expect to see some kind of development from continuous sort of development from the 17th up to the 19th century but in fact what we really see is a sort of 200 year delay so microbiology doesn't really come to exist until the 19th century microscopy is not important in

most people studying the human body or studying the natural world are not really using microscopes the other thing you'd expect to find if it was if microbiology was being driven by the development of microscopy is that in the 19th century it was the microscopists who create microbiology, but in fact it's a chemist and people you could call physiologists, really.

So I guess the key point is that it's not what microisms look like, but their functions, what microorganisms do that created microbiology. And the people who could begin to unlock the secrets of what microorganisms do were chemists and people with laboratories and doing experiments rather than people looking through lenses at form rather than function, so to speak. Can you tell us how this second phase, as it were, got going, who you might pick out? Can you tell people about that and pass on the significant universe? Semmelweis introduces another twist into the story,

which is there were people who weren't using microscopes at all, nor did they use laboratory experiment, nor did they use chemistry. They simply used medical observational skills in ways that later helped to make plausible the idea that, for example, microorganisms cause a disease. So Semmelweis was a doctor in Vienna in the first half of the 19th century, so this is before Pestor.

He was making his observations when Pester was a kid, basically, in France. And he was a doctor, and he happened to work in two maternity wards in the Vienna hospital, and one of them had a very high mortality rate from childbed fever, and the other one didn't. And the ward with the high mortality rate, with a lot of women dying at childbirth from a feverish condition, that was called childbed fever. That was also the teaching ward.

And teaching ward meant that was also the place where people were doing post-mortem dissections in order to learn about the body afterwards. And people all knew that the dead body was a source of bad odors and of putrefaction and that people understood that this was in some way possibly related to disease and danger. And he surmised that the high mortality rate

in that teaching ward where the students were going back and forth between the beds and the beds and the dissection table had something to do with these rotting bodies in the dissection room. And so he instituted a hand-washing routine in this ward, and he brought the mortality rate down dramatically with this. And this was unfortunately not met with universal acclaim as a major medical innovation because it implied that disease was being spread by the doctors. Did that discovery first through observation and common sense people would say,

but still takes a great mind to find common sense at the right time. Did that have an influence on people like Pasteur, or did you just sort of die in the dark? It certainly was not in no way led Pasteur to begin to study either disease or microorganisms. However, once people began to use laboratories to study microorganisms and to begin up, build up a picture of microorganisms in disease, they could look back on these kinds of statistical results, which Semmelweis was able to publish and say, that really adds to our argument.

Okay. Can we talk about what Louis Pasteur brought to it? Most people think he is one of the two or three great giants of this study in the 19th century. One of the things that Pasteur was is he was an incredibly good experimentalist. And Pasteur, I mean, we know him in many ways, but we know him for pasteurization, for example. And that was an interesting one because Louis Pasteur started off the concept of the germ theory of disease that they're these small microscopic organisms which give rise to disease. And he tried to prove that by showing that life didn't arise

through spontaneous generation from non-biological life. You didn't just get it by doing wonderful experiments where he got flasks, where he took the neck of the flask and he bent it into a sort of U-shape, a swan-neck flask, as they're called. And he showed that if you boiled that flask up, a nice rich nutrient medium, and then it became sterile, free of organisms. But in that little bend in the flask, organisms could go in and settle in the

bottom of the bend, but they couldn't actually get into the nutrient medium. And then he showed that if you tip the flask, so the nutrient went into the little bend and collected the microorganisms that had floated in there and popped them back into the nutrient medium, then he would get growth, which he could observe using the microscope. But where, I'm not saying this shot him to fame, but Napoleon had a problem around about the, the medium. 18th century and that was that his sailors rebelled because when they went on sea voyages, their wine started spoiling after two or three weeks or whatever on board. And this was a big problem for Napoleon.

So he called upon Pastor and asked him to try and solve the problem. And then Pastor did use a microscope and looked down the microscope and saw a number of organisms and he actually became able to predict what the taste of the wine would be like depending on what organisms he saw down the microscope. So he determined that some of them were responsible for spoiling the wine, and he also inferred that some of the other organisms he saw, which turned out to be the yeasts, were actually responsible for the fermentation

that gave rise to the wine in the first place. And his way of solving Napoleon's problem, or the sailor's problem, was to take the wine and to heat it up to a temperature that would kill off the spoiling organisms, but wouldn't taint the flavour of the wine. And that's the process which we now understand as pasteurisation, which we still use today.

Can we come to another great figure of that time, John Dupé, Robert Koch, can you tell us what he brought to this study? Well, I suppose, I mean, certainly the way come to Seacock is in terms of really defining a horrible word, but I can say paradigm, and people debate whether this applies in this case. But it seems a very good example because it really, even to this day, it's still set up ways that people think of as fundamentally how you do microbiology.

And he's come to be known for what called Cox postulates, and as with everything in history, I gather, he probably never stated them or anything like that, but still, that's what he's gone down for defining. And these say that the way you investigate a disease is you extract from sick organisms, a microbe that causes the disease. This microbe should be present in every case of an organism that has the disease.

You should then be able to culture the microbe and then inoculate healthy organisms with the disease and cause the disease. And that's the kind of criterion for having identified the disease. And then, of course, you can investigate how you might kill the microbes and so on. So this is sort of what he's laid down as the way you, do microbiology. Sorry, please go on. Well, I guess I was just going to say, I mean, as in so many of these kind of defining

ways of doing something, I mean, it's been enormously productive, but also enormously restrictive, I think, in the way people have subsequently done microbiology. And in particular, the notion of the pure culture, which, of course, could be related to a lot of other things that were going on in biology. I mean, pure cultures were very important for Mendel's work, you know, in quite different area. But the notion that you should produce a pure culture as part of the kind of paradigm of doing microbiology is very problematic because the way things now look to us, actually the vast majority of microbes can't be cultured. In fact, I mean, as people say, maybe only

1% of microbes can be grown as a pure culture in vitro. So in a sense, it's limiting the scope of microbiology in an extremely narrow way by laying down this idea of how you should do it. So Andrew Mandelsohn, how scientists, we've got these two people setting up the study, as it were. Let's leave it at that in this for this conversation. As John's just said, only 1% of microbes can be culture that is worked on in laboratory. So it's a very small, to put it mildly, a very small basis. How do scientists grapple with that fact that they learn? and that they can only work with 1%,

and the whole business might be completely different, really, because the 99% are getting on with it. Yes. Well, there are a number of things to say there. I mean, I suppose the first one is that at that time, they didn't realize that it was just 1%. And in any case, it didn't matter too much because the ones that they were able to culture

happened to also be ones that they identified as being causative agents of important diseases of animals and human beings. But there were problems that they had to grapple with, such as the problem of, as was just mentioned by John, in order to try to demonstrate this causal relationship, you need to be able to reproduce the disease in an animal by inoculating, injecting the animal. But this proves not to be possible, really.

So this completely fails with this very important disease in the period of cholera. And as a 20th century scientist pointed out, if you're talking about tuberculosis and looking for an animal model, mice don't cough, right? But there were other problems as well that arose which show us that it would take quite a while for or show us that germ theory wasn't simply demonstrated

and that was the end of the story in the 1880s. And those problems were that two things. Number one, disease-causing germs were found to be widely distributed in the healthy part of the population. and number two, there were lots of people who seemed to have a particular disease that a clinician could say, well, this person has this disease, but they couldn't find the germs in them. And the first of these things was dramatically demonstrated by a public health expert in the period

who, in a sort of public experiment, swallowed a pure culture of these deadly cholera germs and survived pretty well, really. And that showed that really what, what, as John said, what had been established were a set of methods and a kind of paradigm for a set of problems, but by no means all of the answers. So we still have many of those problems with us today. This lack of cultureability is a really interesting thing in terms of microbiology.

I mean, to put it in another way, lack of microbes you can experiment on in a lab. In the lab, yeah. That's what we mean by cultural ability. By cultureability. I mean, obviously they grow fine in the environment, but we bring them into the laboratory, and as you're saying, we can perhaps culture, less than 1% of them and grow them in the laboratory.

Why that's amazing in a way is because all our knowledge of microbiology is based on that 1%. 99% which are out there and doing something we know nothing about. So, I mean, it really is the hidden universe. It's unbelievable the diversity that we've got out of there. And if we look at something like soil, if you go outside and you take a pinchful of soil in your hands, that pinchful contains more microbes than there are people on the planet. And we don't know what they're doing. We don't know what potential they have.

It's a fabulous, unexplored environment where we, you know, if we had the tools, we could look at them. And actually, probably more recently, the last 10 to 15 years, we've established a new set of tools. So this is almost like the molecular microscope instead of looking at the optical microscope, which Huck and Van Lohen-Hook demonstrated. We now have a set of molecular biology tools whereas instead of trying to grow them up, all we're interested in is their genetic information, what makes them tick.

And so instead of trying to multiply them up in the laboratory, we dissect them, take their genetic information, and that gives us the information about their diversity and abundance. But just before we move on to what develops from all that, we're still at the stage we could say where somebody like Edward Jenner can use the microbes to bring health. Okay, Jenner

was a, he was a country boy and in the country he was once told, I think, by a milkmaid that if she would never get smallpox because she was a milkmaid and she'd suffered from cowpox which gave her a small rash in the hands and that was about it. And Jenna remembered that,

trained as a doctor, went back to a country practice. and again and again he heard from, I suppose, his male friends that if you wanted a pretty wife, then marry a milkmaid's complexion. Exactly. She was never going to end up being disfigured with these pock marks and so on. And he remembered what he heard from the milkmaid about getting the cowpox. So he did an experiment, which is utterly terrifying in today's terms, which was... You wouldn't be allowed to do it in today's terms, well?

You certainly would not. So smallpox would not be cured. Only the ones. He got an eight-year-old child, a young eight-year-old boy who was a healthy young boy. He deliberately inoculated him with cowpox, and he was fine. And then eight weeks later, he deliberately inoculated him with the lesion, the scab lesion that you get from somebody suffering from smallpox. And the boy survived because he'd been inoculated by the previous exposure to cowpox.

And that was the basis, if you think, I mean, past, then went on to develop that much more. But that was the basis of vaccination. And we still use that today. And it was widely adopted because it had a significant impact on health and the diseases that people died from. I mean, if you go back to, it's not quite as far back as Jenner or Pasteur, but even in the early 1900s, the major causes of death were influenza, tuberculosis, gastroenteritis.

That's what most people died from. whereas nowadays hardly anybody dies from microbial diseases. We all die from cancer, heart disease and stroke. And even things like accidents, like accidents at work, you've got a greater chance of dying from than you would do from a bacterial disease. John Gibray, can you tell us about microbes communicating with each other? Can you tell us about that and what implications that might have? Well, this is part of, that I mentioned in failing to ask your very first question,

about unicellularity. I mean, microbes are enormously social to the extent that it even becomes problematic to think of them as isolated single-celled organisms in a way. And I guess there are actually two really fundamental things that we know about that they do to organize themselves in these complex communities that they tend to live in. and one which I think we're really only beginning to understand is, as you say, communication, chemical communication. So, for example, one of the better studied forms of communication is that they do what is referred to as quorum sensing, so that a group of microbes are able to determine when they reach a critical size, a critical number, that enables them to engage in some kind of interaction with the environment and they do this through transmitting chemicals

that obviously other microbes are capable of detecting. Because the other thing that sometimes is a response to this and again is really subverting in many ways our whole conception of biology is that they exchange DNA among themselves in the most remarkably promiscuous way and we know three different mechanisms they use for doing this. And in fact, it's likely one of the things that they do in response to communicating with one another is past little modules of, for example, things like antibiotic resistance

is known to be spread among microbes by what are actually called DNA cassettes that they pass on from one microbe to another, which enables them to process antibiotics and resist the effect of them. I mean, they're cooperative in ways that we're only really beginning to, I think, to perceive and understand. But there's still the antagonistic part, as I understand in Andrew Mendelsohn. There's still microbes attacking each other, and we can bring antibiotics to bear on that, can't we? Yes, well, antibiotics comes from that, actually. I mean, when most of us, if we ever have to take an antibiotic for something, we think of it as, you know, a pill that's come out of a factory from

a pharmaceutical company. But of course, what we're really doing is using microbial relationships for our own purposes. So penicillin is named after the name of the mold, penicillium, a genus of mold, which excretes a substance that is antagonistic or inhibitory or kills bacteria. And so there is the communal size. of microbial relations and there's also the antagonistic side of it of those relations and we've made good use of it. So we're coming into, at this time when we're coming in the 20th century,

the study of microbiology is becoming more serious and more extensive and it's one of the great, as you said down, it's one of the 99% to go yet really. Can we go back to what John Dupé was saying about the way that the DNA shifts and what consequences, if you can kick us, off on this paragraph, John. What this is going to

tell us say about current theories of evolution? Can you just take us in that direction? Yeah. Well, you can sort of suggest that our theories of evolution have been very much based on people studying, for example,

birds, which, as they suggested, very peculiar organisms. I suppose the thing that is most fundamental is that when we look at microbes, we find the notion of the kind of isolated lineage in which evolution takes place that we think of when we talk about...

An isolated lineage means guerrillas mating with gorillas and not with elephants. That's right. And so we can study the development of gorillas through gorillas. Absolutely. And we theorize evolution as something that happens within that context. We define the species as the unit of evolution as something which is genetically isolated from everything else. And that's kind of a nice, neat way in which we can look at evolutionary processes. But then we realized that, as Anne said, 80% of evolution,

there were actually only these microbes. And we realized they don't live in isolated lineages. They just shuffle DNA around in a quite promiscuous way. And in fact, I mean, this is why I say viruses are so important, because then we start looking at viruses. whereas they're not only one of the ways in which DNA is carried from microbial cells to other microbial cells. And by the way, quite different kinds of microbial cells. Right across all these three domains of life, viruses can carry DNA from one kind of cell to another.

But we actually find that our own cells, if we look at, as we start to analyze what we find in the human genome, i.e. the genome of that 10% of us that we call human cells, at least half of it originates from viral, you know, viral insertions into the genome at some historical point. Now, at this point, we're fairly well isolated, but probably not that well isolated. So the whole, it looks at there's a great flux of DNA flowing through life, and this picture of a kind of branching tree

is becoming more and more questionable, even obsolete. because the classification is employed, let's say, by Darwin now seem a tiny, tiny part of the mass, the mass now being mostly microbes. What does this say, Anglover, about the classifications of life, about the theory of evolution? Well, what I think microbe... If you want to study the history of life on Earth,

study microbiology, because they're almost like living fossils, because what you have is an example of all sorts of life that can live in all sorts of environments. So wherever you go on the planet, if you went to a deep sea vent or into a volcano or into your car radiator or wherever, there will be microbes living there. And if we look at the genetic information from those microbes and we sequence it, and it's some 15 or 20 years ago probably when the first microbial genome was sequenced.

And we've got a bit of an advantage there because they're much smaller than our genome, so it's quite easy to sequence them. and you find that there are some bits of information there which are unique to that particular microbe and we'll distinguish it from another one and there are other bits of information which are very similar so all microbes have particular sequences of genetic information which they need to survive

and in fact we also have these particular pieces of genetic information and you can use that bit of genetic information to start classifying life So that's how you do your taxonomy. So instead of what was done previously by observation, by looking at things and saying, well, that looks similar to this. So it must be related to that. And then working out an evolutionary tree from observation. This is done using molecular biology now to look at these sequences and say,

what percentage similarity do I have to this other organism? And that builds up the evolutionary relatedness between them. Is this Andrew Mandelson, would you say this is in some way a challenge to the theory of evolution, the Darwin's theory of evolution? I think that's for Anne to decide. Or John, really. John. Well, I'd just like to just pick up a little of what I was just saying, because what she's describing, I'm correct, is I mean, you can use molecular methods to trace a lineage of cells. you can have very fascinating information

about how the cells descended and branched and so on. But it becomes, I think it seems to me in a way much more questionable what you're doing with that because the cells that you trace and you put in this evolutionary or phylogenetic tree where they are on the tree doesn't necessarily tell you very much about what they do because all the other genetics,

the genetic information, coming from all over the place. So you actually have a web of relatedness, and it becomes much... So if what you think of as classification is classifying things so you can find out what they're like, what they're likely to do, then this phylogenetic evolutionary history

may not tell you very much. Does it follow the same rules as it were, the same pattern that Darwin laid down, to the way the microbes develop, or our osloat, as it were, including plants. Now, in a tiny, because of the micro, are they following a different pattern of development? It seems to me that they probably are.

And if they are, that obviously not challenges, adds to, it does something about the theory of evolution, which obtains now for a much narrower, smaller, tinier field, and we thought because these narrower, smaller, tinier creatures, sort of challenged it. I think that's right, certainly insofar as certainly there's this notion of thinking of branching lineages. It really is something that only applies this very small area. I think there's another thing which is, of course, Darwin had an awful lot to say about cooperation as well as competition.

But as we look at microbes, it starts to become clearer that symbiosis, cooperative living, is absolutely the norm, even for us. And this is why it's important that we're actually, in a sense, part of this microbial world still. I mean, some people like to actually kind of take this a little bit further and say, well, cow is really just a great. great big fermenter and a pre is really just a great big kind of umbrella stand for the microbes to get up near the sun so I mean you can

you can take a perhaps reductive view of this as actually seeing us in relation to the microbes that live in us and Andrew Anderson where do you think we are with the study of microbiology at the moment I mean it's very new

compared to study of physics and mathematics and And is it, as Anne seems to suggest, on the brink of a more enormous discovery, is this 1%, as it were, using this metaphorically as well as realistically? Where is it going, this study? More and more people are getting involved. It seems to be more and more important. Now you take it up.

I suppose as a historian I always have to look to the past in order to say anything about the future. But I suppose the one observation I would make is the way, in which some of the themes that we're talking about, certainly not the exchange of DNA cassettes, but some of the themes that we're discussing are right there at the moment when Pasteur is creating microbiology. So we have to remember that we touched on this earlier,

but it could perhaps be filled out a little bit more, that he spent, before he even came to study disease, and before he got interested in the spoilage of wine, What he was really doing was looking at the sort of productive powers of microorganisms in wineries and breweries. And so he actually had, he didn't use the word ecological because it didn't really exist. But he had an ecological and he did use the word cosmic vision of the importance of microbial life for all of nature as well as for us. So even in your introductory comments, he said that, yes, they cause disease. but if they, you said something like if they were to disappear, life would grind to a halt.

That is virtually a quotation from Pasteur, although we don't realize this anymore. So he, in fact, this is how he got his first government-funded laboratory. He wrote to the Minister of Public Instruction and said, Monsieur de Minister, I am going to solve the problem of the cycle of life. So I think it's interesting how, in a way, this sort of 1% and the medical sense that we have of microbiology is almost like a kind of episode for a period of, say, 50 years, 60 years,

before and after which, this much bigger picture of the importance of microorganisms and what Pastor has called this cosmic significance of microorganisms for the planet and for nature and for living things is the frame within which we need to understand. understand the significance of this science. Finally, I'd like about each of you.

What do I just think microbes will be of most help in the future? Will they be used, manipulated to special micro-bred clearers of oil pollution and so on and so forth? Can you see what sort of futures do you see? Starting with you, John. Well, I think that's one clearly important area. I think the possibilities for this sort of bioremediation are enormous. Perhaps another thing just to mention, though also is just if we look at biology generally, sometimes we underestimate or we don't notice how much what we can do with the sort of big things that we're more interested in

actually depends on microbes itself. So all the genetic engineering we're doing is really learning to do what microbes have actually been doing for billions of years, which is reorganize their genomes in ways that adapt them to do different things. Break things down, recycle the process. So, I mean, our ability to do genetic engineering, to do genome sequencing, is all actually using chemical tools that we found in bacteria. Probably will find a lot more of these tools. And like bacteria, as they say, some scientists will say,

constantly are engineering their own genomes. advances in kind of biotechnology, both within microbiology, towards the sorts of things you're talking about, like bioremediation, and in dealing with plants and animals, is likely to depend on understanding microbes better. Andra Mendelton.

Again, referring to the past, I suppose. I think that the areas that will continue to be meaningful, and productive in microbiology are probably the same as the ones that have always been there, strangely enough. And that is to say that there will continue to be a technological human use dimension that goes back to the study of fermentation. But there will also be a dimension of what we're referring to as understanding biology, evolution, heredity. that also really in a way

that's a meaning of microbial life that goes back to the also to the 19th century when a lot of the attention that was given to people like Pestor was given to them for their arguments about a spontaneous generation which and the framework for that

was very much how did life begin and does it develop or does it develop in this way or that way so those theoretical biological scientific meaning and then also the human uses of microorganisms, I think, in a way, will continue to characterize the science as they have already in the past. And finally?

There is a very long list of how microbes might open up new doors for us in the future. I think microbes are intricately involved in controlling our climate, and so they might have roles in helping us to mitigate the current climate change that we're looking at. microbes produce drugs and will produce drugs for us. Microbes will produce fuel cells and perhaps will give us a sustainable way of generating energy in the future. There's almost anything that you might imagine because of the diversity of microbes, they can offer potential pieces of interest in terms of technology and solutions to the problems that we create. And perhaps comfortingly in a way, they were around first,

We've been around for a very long time and they'll be around when we're long gone. Well, I don't think that's a great deal of comfort, but still, we'll draw on the programme to a gentle, let's slide the coffin in at that point. Thank you very much, Anne Glover, John Dupre, and Andrew Mendelsohn. Next week we'll be talking about epistory literature, and thank you for listening.

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