Understanding Life: Biology's Fundamental Principles

Life, as understood by the speaker, is defined by the maintenance, growth, organization, reproduction, heredity, and diversity of living organisms.

### The Fundamental Principles of Life
* - Living organisms are extraordinary entities that can **maintain themselves, grow, organize themselves, reproduce, and pass on characteristics to their progeny**. 
- They are also **highly diverse and difficult to define**.
* 🔬 Life is based on chemistry and physics. It can be considered as a **complex chemical machine** with different chemical microenvironments within cells carrying out **specific reactions**.
* Information management is crucial to understanding life. DNA serves as a **digital information storage device**, while gene regulation involves **feedback control mechanisms similar to electronic circuits**.
* 🧬 Life evolves by natural selection through **reproduction, heredity, and variability in the heredity system**. All life on Earth is **fundamentally connected and interdependent**.
* The cell is the **basic unit of life**, separate from the environment but in communication with it. Polymer chemistry, especially carbon-based chemistry, plays a **central role in life**.
* 🌌 "The principles underlying life are likely to be found in other life forms, should they exist elsewhere in the universe. As the only known planet with life, we have a **special responsibility to care for and understand life on Earth**."

[Music] What is life? That's going to be the question that I'm going to consider this evening. It's one of the most fundamental questions in biology. I think many would argue it is the most fundamental question in biology. I'm going to talk mostly about life on planet Earth, but the question also makes us think about life elsewhere in the universe should it exist, perhaps built in different ways from that on our own planet. Before I begin, I want to stress something: living things are extraordinary. They are completely extraordinary. They are entities that can maintain themselves, they can grow, they can organize themselves, construct themselves, reproduce into two identical copies or close to identical copies, they pass on their characteristics to their progeny. They are also extremely diverse. And it so happens, which is why this lecture is difficult, is that life is very difficult to define. Now the approach I'm going to use is to examine some of the great ideas of biology, five great ideas of biology, which characterize the attributes of life. I'm

going to give you a little history of where those ideas came from, and then I'm going at the end or towards the end of my lecture to derive from those five great ideas some core principles, with the hope of getting closer to defining what life is. I hope you noticed the careful way I said that sentence, close hope of getting closer, rather than actually answering the question. Now, of course, I'm not the first to ask this question. It's been wrestled with by scientists over the ages, and my first slide here was is the first page of a very influential contribution published by scrolling her heel the uncertainty principle, a physicist who dabbled in biology in his later life and published a book. This book here in 1944. It's a 75th anniversary of this book based on lectures he gave in Dublin in 1943. He was particularly concerned with how living organisms maintained order. As a physicist, he was particularly interested in the second law of thermodynamics, and he wanted to know how life could escape.

the decay into chaos, that is of course enshrined in that particular law, and how to do it across generations. This is two quotes I've taken from that 1944 book, which actually is quite a good read. I still read it occasionally, and in fact, it's on my kitchen table because of this talk at this very moment. The first, there an organism's astonishing gift of controlling a stream of order on itself and thus escaping the decay into atomic chaos. The second law, as I just said, he's also interested in how this order displays the power of maintaining itself and producing orderly events, and this is what I'm going to be talking about in the rest of this lecture. I'm going to start it with the cell, the cell as the basic unit of life. As I said, I'm going to give a some background to this, some history. The soul was first observed by Robert Hooke in and who he published his observations in 1665, and you'll see here on the left the black and white picture of what he saw. He took a piece of cork

cut it with a razor, put it under a microscope, similar to the one you see in this picture behind me, and saw lots of little boxes. I put on the right there a modern scanning e/m picture. It's pretty similar, really not too much advancing 350 years. What he saw there were rows of boxes. He called themselves after the Latin cellula for small cubicle. And soon after him, a Dutch Draper Lowen Hooke lived in Delft, quite a humble man, made even better microscopes than then Hook. And he scraped between his teeth and put it under one of his microscopes. And what did he see? He saw bacteria, the very first observations of single-celled microbial life. The charming pictures here, can you see? I think it's Figure B. Obviously, they were swimming around and did a loop-the-loop there, as you can see. Lone Hook was a bit disturbed by this because he's rather proud of his clean teeth. And I think was disturbed at discovering all this life in between his teeth. He sent all his observations to the Royal

Society has a thousand letters describing his observations. We don't have a reliable portrait of him, but he was the neighbor of Vermeer, the famous Delft painter. Vermeer usually did two paintings of scientists, a geographer, and an astronomer. And I like to think this might be Loon Hook that we're looking at here. I should say, as I am a scientist, there's not one ounce of evidence in favor of that. Now, although cells were observed just before the beginning of the 18th century, science developed over quite a long time, a couple of centuries, in fact, and eventually led to two concepts. The first concept was stated by Theodor Schwann, a German zoologist. He published in German. This is a translation here from 1839. We have seen that all organisms are composed essentially of like parts, namely of cells. In other words, the cell is the basic structural unit of life. Very critical. The second observation, the second concept I want you to be aware of, a few years later.

another German Rudolf Virchow, a politician and scientist, founder of pathology. By the way, he stated, It's a little different. Every animal appears as a sum of vital units, living units, each of which bears in itself the complete characteristics of life. In other words, the cell is also the basic functional unit of life. All growth and development of life is, in fact, based on the cell. Here's a fertilized mammalian egg with the sperm bashing on the door of the egg. And if I haven't inspired an interest in you yet, let me remind you all that you once all looked like this. You were once all a single cell. Through growth and repeated reproduction of cells, we produce here a mammalian embryo, and then eventually ourselves. Now, what do we learn by cell from this discussion about cells, about life, and what it is? This is a modern multicolored version of cells. Well, a couple of conclusions. The first point is, as I have just said, as the basic structural and functional unit of life, it is the simplest entity.

which exhibits the characteristics of life. It can maintain itself, it can grow, it can self-organize, it reproduces, and it has heredity. What this means is if we try and simplify the discussion, that if we can understand cells, then we're very close to understanding life because it is the simplest entity that has the characteristics of life. And that means cells are going to figure quite a lot in this talk. But what I say about cells applies to living organisms as well, including ourselves. The second point is that the cell is bounded. It's separate from its environment. You saw that obviously with the microbial cells, the bacteria, but it's also the case for all our cells, which are all surrounded by a membrane and separate from the rest of the environment. Why is that important? It's important because it allows order to be generated within the cell, giving rise to complexity without contravening the second law of thermodynamics. It's an isolated system which creates order as a consequence of further disorder in the environment. So in fact, the problems with

second law of thermodynamics that physicists always worry about simply isn't an issue because of the cell. As a bounded entity, although it's a bounded intimate entity, it has to be in communication with the environment. It's semi-permeable. The membrane is literally semi-permeable, and it builds up within itself components that it takes from outside in its environment. It produces Monteux. It takes them off a concentration gradient. It requires energy to do that, but the important point is that being isolated from the environment, complexity can arise. So we don't have to worry about the problem that certainly was of great interest for Schrodinger. However, he said something a little more. He was interested in how that order is maintained generation after generation, and he came up with the idea that maybe there was a code script. And this is another quote from that little book: These chromosomes, we kind of come to chromosomes in a moment, containing some kind of code script. The entire pattern of the individual's future development in function is related to a code script.

he goes on to speculate that it may be what he called an a periodic solid. It was trying to explain how order could persist, and he speculated that that code script underpinned the development and function of the living organism. Now, this is essentially the second great idea of biology I want to talk about, which is the gene as the basis of heredity. Now, this came about from work from the abbot of a monastery in Bruno, now the Czech Republic. He was a monk when he did what I'm about to describe but then became the abbot. He was trained as a physicist and he got very interested in doing crosses with plants to try and understand heredity and how characteristics were transferred down over the generations. I visited it in 1981 at the height of the Cold War. I took this photograph of his garden. Actually, it was quite a big gun wasn't used for growing things to eat. It was used for growing his plants for his experiments and next door to it was a greenhouse, unfortunately dismantled of.

similar size. I mean, frankly, there was major investment from the Justinian monastery in scientific research. Quite extreme, ordinary in the 1860s. And from that research, he came up with the laws of genetics. And he did that and he was successful where many others had failed for several reasons. He did trial crosses with a range of plants and decided only to work on those which he could make sense of. You could say that he was cheating in some ways, but actually in biology, which is so complex, you have to choose material and problems that you can solve. Remember, science is the art of the soluble, and it's no point wandering around if you can make no sense of it. And he ended up choosing the P. And he chose the P because it was easy to characterize the different traits of the plants. I'll show you some in a moment. And because he was a physicist, he counted what he saw. He was quantitative. So you can see here some of the different characteristics. Here we have flowers of different colors. We have tall

plants short plants we have seeds that are not shown here which are rough or smooth now because he worked on peas and these different characteristics the differences were decided by single genes it became easy for him to analyze what they produce for the very simple ratios that you may have read about in school like three to one one to one nine three three to one and what you need to take home from that is simply that he could explain it all if what was the basis of this were particles particles that were being segregated during the during the crosses that he was carrying out these particles a particular model for inheritance of what we'd know as genes today interestingly nobody sublime didn't notice of what he published it lay there for 35 years and then it was discovered by three geneticists at roughly the same time who got the same results they weren't always so generous in acknowledging their predecessor and there's a story around that but I'm not going to sully science by telling you about it all you have to conclude is

that they're human beings just like we are today, and we're not perfect. Then it was taken very seriously, why we don't really know, but several things happened between 1865 and 1900. 1900 and - the first is that chromosomes were discovered. This is a late 19th-century picture of chromosomes in onion root tip cells, which is where I first saw cells when I was at school in Northwest London. Did a squash and saw these chromosomes here, and these chromosomes were postulated to be the place where genes were located, which were being separated every time a cell underwent division. Then of course, that led subsequently to the idea. In fact, the fact that these chromosomes and genes were made of nucleic acid DNA that was discovered by Avery working in the Rockefeller Institute in New York, which I led for eight years from years ago actually, and that showed that DNA was the chemical basis of heredity. Did a beautiful experiment took a DNA from a pneumococcus, a bacterium of a not of a.

virulent strain. Basically, dropped it on a non-violent strain and transferred virulence from one to the other, and it was DNA that contained that. And that's what showed it was DNA was the hereditary material. And then of course, what we see here is the double helix, the famous double helix structure involving Crick and Watson based on the experiments of Franklin and others like Wilkins. And we know, and I shall refer to it again a bit later, that this is the basis of heredity. And finally, Crick himself postulated what he called the central dogma of molecular biology where the information, which I shall talk about more, stored in DNA, is transcribed into another nucleic acid, RNA, and then translated into protein. And that's going to form a central part of what I shall say. This is the basis of Schrodinger's code script. It explains the permanence of the heredity because it's replicated every time a cell, and therefore organism, divides. So living organisms, and now we have to think about principles, are based.

at least on earth, nucleic acids encode information and they can be precisely copied because of pairing between bases that make them up. And again I shall say a little more about it before we do that. Though this discussion has introduced two new concepts that I want to introduce to you. The first is chemistry. The chemical aspects of living organisms are critical for understanding life, life as chemistry. The second concept is the importance of information encoded in those molecules. And these are the two ideas we are going to discuss next. And I'm going to start with life as chemistry. Basically, life is based on chemistry and physics. It's the mechanistic basis of life. I have to stress that because for many years, actually a couple of thousand years starting with Aristotle, scientists thought that the complexity of life was so great that it could not be explained by the laws of chemistry and physics. They proposed vitalism, that there were vital laws that weren't based on chemistry and physics and that were necessary to explain that.

complexity. It took work by French chemists to overturn this initially. Lavoisier, although his work was terminated because he was guillotined because, unfortunately, as well as being a scientist, he was a tax collector for the ancient regime so he lost his head. And then it was taken over by Pasteur, the famous Louis Pasteur, who was working on an applied project on why sugar beet fermentation went wrong. He came to the conclusion that it was all to do with chemical products being made during fermentation and came to the following conclusion: that fermentation was a physiological act yielding chemical products for the cell. And he could then advise the sugar be fermenters as to how to do it. And then he made a general conclusion: chemical reactions are an expression of the life of the cell. In other words, he was postulating if we want to understand life, we have to understand the chemistry that goes on in life. I can summarize that in a different way, which is that living cells, back to cells again, can be considered as a

chemical machine a complex chemical machine including also physical processes as well. However, it is a very special sort of chemistry that we see in living cells on this planet. This chemistry is based on carbon. Carbon is made inside stars. It's the fourteenth most common element in the universe. We are basically based on stars, a rather interesting idea. Now what's important is that each carbon atom can form four chemical bonds, linking it to other atoms, and it can use two of those bonds to link to other carbon atoms to make up chains, a sort of polymer. You can see that here. There's a backbone of carbon that makes up a linear polymer, but then it has two free bonds which can form bonds with other atoms such as oxygen, hydrogen, carbon itself. And this means that there's a variety of different chemistries that can be put on top of this basic polypeptide chain. And that's because it's made of a chain of amino acids which are of carbon and connected by nitrogen. And there are 20 different amino acids that are used by life.

they had different chemical characteristics. Some of them are bulky, some of them are small, some of them are acidic, some of them are basic. That is their negative or positive charges. Some of them like water, some of them don't like water. And all of this can lead to a wide variety of chemical properties. And because you can build up extremely long carbon chains, maybe I mean thousands of thousands long, then you can produce very complex structures, which can also fold up into a three-dimensional structure. Now there's a lot going on here that is really important to emphasize because what we hear, see here, starting off with a simple carbon polymer made up of different amino acids, you can make elaborate molecular structures with a variety of different chemistries that can be put there. That leads to a huge variety of chemical machines, and these are the basic workhorse of life. These make up the enzymes that change other chemicals into different chemicals. They can build up molecules, they can break down molecules, that's as part of metabolism, which is critical for the functioning of life.

these chemical machines are so efficient that they can operate in very gentle conditions. We sometimes try and mimic it in rather more extreme conditions, in for example, industrial chemical plants where we have high temperatures and high pressures and an extreme conditions. But these can operate in very gentle conditions. Why is that important? It's important because it means that within a cell, a tiny cell, many hundreds, in fact thousands, of chemical reactions can be occurring in a very restricted space. Because you're not having to have high temperatures or pressures, you can have very gentle conditions. However, these reactions can only occur if there's different chemical micro environments. So if we look at a metabolic map here, each of those dots on this map, I had to learn this as an undergraduate, that's why I took all the names of, but all these dots are different chemical reactions and they're all occurring simultaneously in the tiny structure of the cell. And if you now look at a cell, you'll see it's extremely complex and but what I want to try and convince you is that actually

this complexity represents the micro-compartments of different chemistries that are occurring in the cells. It's not how it's normally explained, and that's brought about by the proteins themselves with different folds making little compartments where a certain chemistry can go on. Assembly of those enzymes which result in components being passed and molecules being passed from one enzyme to another different membrane components compartments as you see here in the cell and even different colloidal structures. What we now call phase separations. So when you look at the complexity of the cell, I want you to imagine it as many hundreds, in fact thousands, of little chemical microenvironments carrying out specific chemical reactions adjacent to each other, connected to each other but separate, and that is needed to generate the chemical complexity of life. Now, there's a consequence of this is that this intricate spatial organization of the cell of these different chemistries must be able to communicate across the cell because if they don't communicate with each other, you can't get order. So you need compartmentation and

separation that you need. Also, communication, what contributes to that, and that comes from physics is that there is a skeleton within the cell made up of different like tramway raised or railway tracks connecting different parts of the cell. And there's little motors working their way through the cell transporting different components from one place of the cell to other places in the cell. And all of these did need energy. And in fact, to maintain the cell needs energy. And there's little batteries in the cell as well, like our chemical batteries charged hydrogen atoms can accumulate behind some of these membranes. And active batteries are transferred through the membrane. The protons are charged atoms, and that produces high energy chemical bonds which are stored for use elsewhere. Communication then is critical, and communication between all these components is dependent upon information and the transfer of information. And that's my next great idea in biology that I want to explain to you as the basis of life. And that is that biological entities are complex systems, and the information management is crucial to understanding how they work.

it won't surprise you that this idea has grown a lot of prominence in the age of computing because obviously information and the man if information it's critical in computing and so there was much discussion of this from the 1940s 1950s and 1960s onwards but it may surprise you to learn that the idea that light is a complex system with these properties has his origins with the philosopher Kant Immanuel Kant around 1800. I found this a big surprise. he wrote a book on on moral philosophy and for some reason got completely distracted into talking about the complexity of life in talking about moral philosophy. in fact although biology can be described in terms of chemistry as I've just done it often only makes sense biologically when that description is translated into the management of information. that sounds a bit abstract but it's important that you get this for understanding life. and there's two examples I want to use to illustrate that and why it's important. and the first is to go back to DNA.

now I've already explained that DNA is made of DNA of course. But is the hereditary material. It encodes information implicitly. Mendel by the way. It was information showing the use. The word code stripped. But the only made sense back in 1865. If you saw it that way. Now the double helix of DNA. And you see here being copied. And because of the DNA is like a ladder of bases. There's four different bases. And G base G will bind to the base C. And base a will bind with base T. So that if you pull that apart. You can get a perfect copy. It's a beautiful thing. And I want you to note that those bases are all on the inside of the polymer. That sort of protected there. And that's going to be important in a moment. Now as I said we can do describe it as I just did in terms of chemistry. But it makes sense biologically when you recognize that actually it's a digital information storage device. I mean that's what we're looking at here a digital information.

storage device. Now, there's more to it than just that because it's organized as a linear script. Now, we often nearly always order information as linear scripts. Think of reading a sentence. It's a linear script. Think of listening to me talk to you. They are linear scripts. Think of computer code. It's a linear script. Think of a polymer. It's a linear script. It is no accident that life is built on a polymer because it is the perfect way of storing information, which is critical for biology. It's critical for information storage. Also, as I explained, it gets better because the linear DNA molecule is very stable. Because the backbone is on the outside, it is not chemically reactive. The chemically reactive parts are on the inside and are protected one with another. So, it's a very stable way of storing that information. However, it can't do anything because it's so stable. It cannot do anything. But remember the central dogma. You go from DNA to RNA, and then you go to protein. And remember what I said about protein. And I'm going to just show you the same slides again. Now.

you still have a polymer. It still reflects information. Each of those amino acids, what you put in there, and the order is determined by the base sequence in the DNA. But now everything is facing outwards, and all the chemistry is facing the environment. So you have oxygen, you have nitrogen, your positive charge, negative charge, much less stable. But now it can carry out chemical reactions. So what you do is you turn stored information in nucleic acid into chemical actions in protein, which are needed for life. So you have a storage device, which is stable, and you have a protein, which are reactive and carry out the chemistry of life. This is really fundamental in understanding life because you can solve the problem of information storage, and you can solve the problem also of chemical action. Second example relevant for information and making sense of biology and information is seen with gene regulation. This was shown by Jacob Amano, who I knew at least a new couple quite well, and they did it by doing beautiful genetics with bacteria, looking at sugar metabolism in bacteria, and what they did.

by abstract genetics is discovered negative feedback control. What is negative feedback control? Well, this is a governor from a steam engine. Now, you may be like me. I sort of understand most machines built before 1900 and almost nothing built after 1900. I took a picture of this in New Zealand. Actually, it was in a steamship, and I went down and photographed it because it was such a beautiful thing. It was found on originally on James Watts his steam engines, and we understand it. The spindle rotates, the balls are thrown out, they lift a valve, and that closes steam off from going into the engine, so it slows down. Then the balls go back in again, and they let steam back into it, and it speeds up. And this is essentially homeostatic s-- it's maintaining a certain, in this particular case, rotation of the particular spindle. And what Jacques will mano did was to use this principle to describe regulation. And here we're looking at something, in fact, not to do with gene regulation, but it's

the same principle what they described. Where we have a chemical AE turned into chemical be turned into chemical see. There's enzymes which are the green arrow and as C accumulates it switches off the enzyme that is catalyzing a into B. And therefore you inhibit making B, you inhibit making C and then C drops in level you lose the inhibition up comes the enzyme between a and B and you'll go back again what this is doing is maintaining by negative feedback a constant source of material. If we look at the bottom one we have positive feedback loop which is the complete opposite when you accumulate C it switches on the enzyme going from A to B. So once you've started this it turns into a switch and you cannot go back you get the principal and life's metabolism and gene regulation is built on these simple principles of this type of feedback control now you can put them together in all sorts of complicated ways and a metaphor is an electronic circuit that you see here and these circuits which we find in life can

produce negative and positive feedback switches, timers, toggles, oscillators, all of which are playing a role in life. Now, it's rather special, just like the chemistry is special. This is special because when we think of, for example, computing, which is of course the same principle, you have hardware and software, yes, but hardware can't change the software. You can make the hardware operate in different ways, but the hardware is wired in. In biology, it's cleverer. It was used, the term was used by Dennis Breyers, assistants, biologists. He used the word wetware rather than hardware because the communication between the different regulatory steps is carried out by molecules diffusing through water, and this means you can rewire the hardware by directing the chemicals to go to different places. So not only can you reprogram it through, if you like, changes in software, you can also change it to changes in hardware. We do not yet begin to understand this complexity, but it's important. Now networks can be very complex. We see at the top here how we like to think about things or to

be more precise how men like to think about things which is linear pathways going from A to Z, but the truth is in biology, it's much more complex. Whereas we all intuitively understand what's happening at the top, there, we don't at the bottom. It's just too difficult. That is because of the next idea I shall talk about, that of evolution by natural selection. Simply means that you add things on to something and make it just more complex. Not necessarily the simplest way to do something, but simply a way of actually a way of actually doing it. But I want to mention one more thing that we don't often think about in these pathways. But if we introduce dynamics into a pathway, that is changes in time, it becomes much richer. And this is a simple example of it. We have a single at the bottom, their pathway, and now we're pulsing information down and either frequently or infrequently. And the output can be different depending on the oscillation, the frequency. This has already been seen. Why am I stressing this? Well, I'll tell.

you why here we see a metaphor for it. Can you see the traffic light? If it's a simple on-off signal, it's either green or red. Not a lot of information. If you introduce dynamics, you can produce the Morse code. That you're pulsing information and now you can write the works of Shakespeare. Now I'm not suggesting the cell is writing the works of Shakespeare, but I am suggesting that we haven't got to beginning to the bottom of how this is all operating in cells. They are absolutely extraordinary and are the basis of how living things work. So what I've explained to you is that the where it's working is through chemistry plus physics. And then management of information. And that's key to understanding what life is. Now my final idea, I can't stop it. This is the most beautiful idea in biology. Evolution by natural selection. It's got two aspects. Life evolves and a major mechanism of it is natural selection. It's a beautiful idea which we mostly associate with Charles Darwin, who you see on the right, but actually the idea of evolution that

is of living organisms changing over time was not Charles as I idea it had been talked about for a century before by French scientists like like Lamarck for example but also erasmus darwin who's shown there on the left who was his grandfather of charles now erasmus is a rather entertaining character so I'm just going to entertain you with one of two things about erasmus he he was a poet and he published most of his science in blank verse. I have a number I collect books from this time and I have a number of books published in the late 18th century and it's all written there in poetry with it with actually very interesting science there as well. He was a dr. George the third asked him to be his physician more than once but he was a Republican and wouldn't do it. He was in favor of female education and he set up a girl school and wrote a book on how women should be taught. It's the first female school in in the UK so I'm told. He got into trouble with his local Dean

he lived in Litchfield for some of his life. In the Cathedral closed, and he had on his coach the motto: everything from Cheryl's. What did that mean? If you open up a shell, you see you would see a sort of formless blob in it. Yeah, and what he was arguing is all life came from formless blobs. But the Dean didn't like it very much and told his richer patients that they shouldn't go to this rather eccentric doctor. And because he actually only charged rich patients, he didn't charge poor patients. He had to paint it out anyway. Very interesting character. And he wrote a number of verses about life changing evolution. But he had no mechanism. And that led to his grandson Charles over there who gathered enormous evidence. First of all, the fact that based on fossil evidence, that there had been evolution. And secondly, during his voyage on the Beagle. And secondly, that he proposed a mechanism. And the mechanism was natural selection. And it goes a bit like this, actually completely.

like this. I don't mean a bit like this. Within a species, there are variants. They have differences. These are due to inheritable differences. They're not ones where if you grow a plant in the Sun or not in the Sun. They are inherited differences, those variants genetically inherited ones which are most successful reproduce more, therefore pass on more genes to the next population in the next generation, and therefore there is selection for changes in characters, and over time that will lead to speciation and therefore evolution, and it also accounts for why you can get exquisite at that, and that we see here. He studied these finches in the Galapagos and came to the conclusion that they were beautifully adapted to weather, they fed on insects or broke nuts, and I put up there a series of tools which are also perfectly adapted for what they do. So, two things. He argued that there was evolution, so all life was related. This is the one figure in the Origin of Species related by descent, and secondly, there is beautiful adaption, and the reason why

this is controversial because it can lead to apparently purposeful behaviors. And if you have purposeful behavior, normally it's easier to describe that because somebody's made it. And there's the famous story of the Reverend William Paley finding a watch on the path. And when he saw the watch, he said this had to be created. And when you see animals and plants perfectly adapted, he argued, therefore they had to be created. But what Darwin's idea of natural selection showed is that you could evolve by natural selection apparently purpose without having to postulate a creator. It would come naturally from that. Now how can it actually occur? Well, it occurs because life reproduces. It has a hereditary system based on genes which determine what life is like. And it has variability upon which natural selection can work. And there I've turned this into single cells. And what you see here is a cell. I hope it's visible behind me, which starts being orange and ends up being red. At least on the right-hand side, you see that. Okay, the idea is this that you have

genes, they're replicated. You pick up an alteration, what we'd call a mutation, and that leads to the coat of the cell being red rather than orange, and red cells have a reproductive advantage. So, over time, you replace the orange population with a red one. Okay, so that's a simple evolution by natural selection. And what we have here is everything you need to evolve. You have and that scene in cells. You have genes, which are the hereditary system. They show variation because they're not copied completely precisely, or they're damaged by external forces like x-rays or sunlight. And then that can lead to evolution by natural selection. I want to finish this part with a quote. This is the old Charles Darwin, the one that we tend to think of, and it's the last sentence of the Origin of Species because he wanted to show that he could produce laws in biology just like Newton could do it in physics. And he states, whilst his planet has been gone cycling on according to the fixed law of gravity, obviously reflecting Newton.

simple a beginning. Endless forms, most beautiful and most wonderful, have been and are being evolved. It's a beautiful ending to a book. I wish I could write like that, but if I did, it would be edited out as being pompous or not entirely relevant. I get it all the time, of course. Now, I've told you about some ideas which are relevant, and I'm about to do a sort of synthesis of them to sum up, but before I do that, I just want to make one or two comments about some life forms which are difficult to know whether are alive or not alive. Of course, there's no simple answers here, but viruses are the critical one. This is a bacteriophage, which is a virus that lives inside bacteria, but we have viruses in us as well. Viruses have a nucleic acid genome. It can be based on DNA or RNA; both work, and they contain that genome, genes encoding components of the virus. They undergo evolution by natural selection. We see that with, for example, how the flu virus

changes all the time. Every generation, so that undergoing evolution by natural selection, which you could argue is a very important principle for defining life. It was one that was actually proposed by Hermann Muller. He was a 19 genesis in the middle 99 20th century because he defined life as living things have properties which allow them to undergo natural selection and therefore do evolve. He simply took Darwin's idea and turned it into a sort of a principle. Oh, I should have said darling wasn't the first person to think of natural selection. Should have said that it was published in 1831 by a man called Matthews who was writing a book about ships timbers and how to grow it. It was only one side so it was nothing like Darwin but he did have the he did have the principle and he wrote to Darwin after Origin of Species and said you might be interested in reading this and Darwin in the second edition actually acknowledged this and of course the story of him also Alfred Wallace who had

the same idea when in a malarial fever is well known back to viruses. Virus is evolved by natural selection so they pass if you like them will err tests but they can only reproduce themselves where it they when they're in the side the cells of other living things. They're completely dependent upon it and they do so by hijacking the cell's molecular machinery to copy the virus's genome and to copy and to make the components that in case that virus. So this means a virus cannot operate separately for another living being its host. It's completely dependent upon another living entity. So is it truly alive or isn't it? Well it's not a clear there's no clear answer about this but I want to say something that generally isn't discussed in thinking about this. It's important to remember that other life forms are also to greater or lesser extent often dependent on other living things. It's not just viruses that have such a dependency. We have many parasites that live inside the cells of bodies or animals or plants or fungi which are

living and depending upon them. This dependency is less total than it is for a virus, but it's in the same direction. Even ourselves, we cannot make all the chemicals we need. We get them from some other living organisms. We can't make certain amino acids efficiently. We have to eat them, and we eat them from plants and animals that actually do make them. So, we are also not entirely independent of other living organisms. Even free-living microbes are dependent on molecules made by other living organisms, bacteria, fungi, and so on, and require glucose, ammonia generally made from other living organisms, particularly plants, which use the energy of the Sun to make biomolecules from simple chemicals, including from the carbon dioxide in the air or nitrogen, which is in turn actually made by bacteria found in the roots of certain plants. What I'm trying to stress here, and as I said, it's not normally sort of recognized, what we really have is a graded spectrum of living organisms, from viruses, which are obviously utterly dependent, through two plants, which are almost completely independent, on a wide range in before in.

the case of the virus. The dependency is strong in other, it's weak, but they all share attributes of life. And we you want to draw the line, it's up to you, and it depends really on your psychology. Are you in your taxonomy? Do you like splitting things up, or do you like putting them together? I like putting them together and saying they're all life, but some require other life forms to fully operate. But actually, all life on the earth is fundamentally connected. It's also fundamentally related as a result of evolution. There is a great interdependency of all living forms on our planet. Now I'm going to finish with principles, and I'm going to describe six principles which I think are important for thinking about life. The first one is simply really a description. I've discussed all of these things before. It's just really to try and put it together. Living organisms have these properties. They maintain themselves, they grow, they can organize themselves. They're exquisite doing that self-organization. They can reproduce, make precise copies of themselves.

have heredity and they're highly diverse. This is what we have to explain. These are the attributes of life. Secondly, life, and this is critical, this is the Muller statement. Life evolves by natural selection through reproduction, heredity, and the variability of the heredity system. Now, by doing this, they acquire purpose. They are entities that can build and maintain themselves, and they have these attributes that allow them to actually do that, and therefore to evolve. But it's the way purposeful behavior can arise without having to invoke a creator. So, it's critical. The third one, the cell is the basic unit of life, separate from the environment but in communication with the environment. This is clearly required to cope with the second law of thermodynamics, and you have a bounded entity that can make complex a complex entity to produce the things that you see on that slide. Principles for life is based on carbon Pullip polymer chemistry. We have lipid membranes built on carbon that separates the cells, hereditary material built on carbon polymers that makes DNA, makes RNA.

we have enzymes built on protein carbon polymers, which easily give rise to chemical reactions. So, polymer chemistry can give rise to complex chemical reactions. Once nucleic acids store information in linear chains of DNA bases, integrating all these functions together is needed. And what a living organism does is to gather information on inputs from within itself and from outside itself, processes them, stores them, uses it to instruct the cells to behave in particular ways. All of this is generated by polymer chemistry. And I don't need to repeat it, but the beauty of it, the stable chemical structure of nucleic acid, chemically inactive, beautiful for storing information, so easily translated into the chemically reactive proteins that we see there in living things. Final point, life is related and to everything else on the planet, and it's highly interconnected. And we are dependent to varying extents upon all other life-forms on the planet. We are all part of an ecosystem. I didn't put it up here, but just to stress, all life has to use energy to organize itself. Their energy ultimately comes

mostly from the Sun through light and photosynthesis, generating high-energy compound. But it can also come from heat from geothermal sources, where there's life-forms that depend upon that. So, this is what I want you to think about in principles underlying life. But I want to end with something a little bit more almost philosophical. I think those principles we've talked about here are likely to be found in other life forms, should they exist, um, in somewhere else in the universe. I think, in particularly important, is polymers because of the way it connects information to chemical reactions. And I think that's something that we is really quite profound if you think about it. But if we go to, if we consider our planet, it is, of course, the only corner of the universe where we know for certain, at the moment, at least, that life exists. And we know, as I started, that it is extraordinary, is extraordinarily diverse. And we can make sense of it. And making sense of it, by the way, is fun. It's, it's rather central.

to our culture and our civilization. I mean, we have to know it. I mean, it's important to us. We know that we're related to the rest of life on the planet. We also know we're deeply connected to the rest of life on the planet. As far as we are aware, we are the only life-forms on this planet who can see this deep connectivity and reflect on what it means. I would also argue we have a particular responsibility because of all of this for life on this planet. It's made up of our relatives, some of them quite distant, but they are all in some sense our relatives, and we are interconnected with it. I want to leave you with this thought: we need to care about life. We need to care about it, and we need to care for it, and to do that, we need to understand it. And I hope you understand it a bit better at the end of this talk and at the beginning. Thank you very much. [Applause]

What is Life? - with Paul Nurse

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The Fundamental Question of Life in Biology

Life's fundamental question in biology is difficult to define due to its extraordinary and diverse characteristics.

Physicist Erwin Schrödinger's 1944 book on living organisms' ability to maintain order and escape decay is a significant contribution to the understanding of life.

The observations of cells by Robert Hooke and Antonie van Leeuwenhoek, and the concepts introduced by Theodor Schwann and Rudolf Virchow, established the cell as the basic structural and functional unit of life, playing a critical role in the growth and development of organisms.

The Significance of Cells and Genes in Understanding Life

Cells are the simplest entities that exhibit the characteristics of life, making them crucial to understanding life itself.

The bounded nature of cells allows for the generation of order and complexity without defying the second law of thermodynamics.

The concept of genes as the basis of heredity, discovered through plant crosses, was further solidified by the identification of chromosomes and the discovery of DNA as the chemical basis of heredity.

The Basis of Heredity and the Role of Chemistry in Life

DNA was identified as the hereditary material through experiments involving virulent and non-violent strains, leading to the understanding of the double helix structure.

Crick postulated the central dogma of molecular biology, explaining the transmission of genetic information.

Chemistry, particularly the role of carbon and amino acids, forms the mechanistic basis of living organisms, with chemical reactions driving the processes of life in a gentle and efficient manner.

The Complexity of Cell Chemistry and Biological Information

The cell contains numerous microenvironments for specific chemical reactions, which are essential for the complexity of life.

The spatial organization and communication of these chemical components are crucial for generating order and require energy and information transfer.

Biological entities are complex systems that rely on the management of information, as exemplified by the digital information storage of DNA and its linear script organization for stable information storage and further protein production.

The Role of Nucleic Acids and Proteins in Life

Nucleic acids store information stably, while proteins carry out chemical reactions necessary for life, bridging the gap between information and action.

Gene regulation, demonstrated through genetics in bacteria, relies on negative and positive feedback loops to maintain a constant source of material and switch on enzymes, playing a crucial role in life's metabolism.

Biology's complexity lies in its unique ability to rewire both software and hardware, using molecules diffusing through water for communication, allowing for a deeper understanding of this intricate system.

The Role of Chemistry, Physics, and Information Management in Cell Function and Evolution

The operation of cells is driven by chemistry, physics, and the management of information, which is crucial to understanding life.

Evolution by natural selection, pioneered by Charles Darwin, is a beautiful idea that explains how living organisms change over time through the mechanism of natural selection.

Darwin's theory challenged the notion of a creator by showing that natural selection can drive purposeful behavior in animals and plants without the need for a creator.

The Role of Genes in Evolution and the Definition of Life

Genes show variation due to imperfect replication or external damage, leading to evolution by natural selection, as explained by Charles Darwin.

Viruses, despite their dependency on other living organisms for reproduction, also undergo evolution by natural selection.

The concept of natural selection as a defining principle of life was proposed by Hermann Muller in the 20th century.

This highlights a graded spectrum of dependency on other organisms, challenging the clear definition of what it means to be truly alive.

The Principles of Life and Their Significance

Life on Earth is fundamentally interconnected and dependent on one another, with the sun being the primary source of energy.

The principles of life include the attributes of living organisms, evolution through natural selection, the cell as the basic unit, carbon-based chemistry, information storage in nucleic acids, and the interdependence of all living forms.

These principles not only help us make sense of the diversity of life on our planet but also carry a responsibility to understand and care for it.