Why is life the way it is? Michael Faraday Prize Lecture – Dr Nick Lane

Good evening ladies and gentlemen and welcome
to the Royal Society. My name is Adrian Sutton, I’m standing in
for the Chairman of the Public Engagement Committee who is indisposed. It is a great privilege to be here to welcome
you and introduce Dr Nick Lane. Before I get on to that, I want to point out
some housekeeping points. First of all, please turn off your mobile
phones; putting them on silent is enough. But we don’t want to hear any ringtones of
any kind. There are no planned fire evacuations; if
you hear the fire alarm it is serious. The fire escapes are those doors and also
the doors in the middle on your right over there. The event is being webcast and will be recorded
for the Royal Society’s archives. We will also be using a speech-to-text service
for people who are hard of hearing. So tonight’s talk is entitled Why is Life
The Way it Is? It is given by Dr Nick Lane, winner of the
2016 Michael Faraday Prize. It is awarded annually for excellence in science
public engagement. It recognises a scientist or engineer whose
expertise in communicating scientific ideas in lay terms is exemplary. Dr Lane can count himself amongst a list of
exceptional science communicators including Frank Close, David Attenborough, Frances Backwell,
Jocelyn Bell Burnell, Marcus du Sautoy, Brian Cox, Andrea Sella and Katherine Willis. Dr Lane is a reader in Evolutionary Biochemistry
in the Department of Genetics, Evolution and Environment at University College London. His research is about how energy shapes evolution,
in particular the way in which the very peculiar mechanisms of biological energy generation
forces evolution down unexpected paths. This perspective has tremendous breadth, cutting
right across the whole history of life from its very origin, nearly four billion years
ago, to the singular appearance of all complex life on earth to the structure of our own
cells and the way that affects our lives and deaths. Nick leads the UCL Research Frontiers Origins
of Life programme and was a founder of the consortium for mitochondria research. His work has been honoured by several awards
and prizes, but he is best known for his books on the evolution of life, which have been
translated into no less than 25 languages. His four books treat the grand sweep of evolution
from the origins of life to our own ageing and death. His books have been critically acclaimed,
being named among the books of the year by Nature, New Scientist, The Economist, The
Independent, The Times, the Sunday Times, The Telegraph and the Wall Street Journal. His book, Life Ascending won the Royal Society
prize for science books. He was described by The Independent as one
of the most exciting science writers of our time. And his most recent book – and I happen to
have a copy of it! – The Vital Question: Why is Life the Way
it Is? even came to the attention of Bill Gates who described it on his blog as an amazing
inquiry into the origins of life. Ladies and gentlemen, I’m pleased to present,
Dr Nick Lane. [Applause]
NICK: Thank you very much for the very kind introduction, and thank you all for coming,
I’m astonished so many people are here, we have an overflow room that is also full. Thank you very much for coming. It is a huge honour. I hardly need to say, the list of winners
of this prize in the past really number many of the people who inspired me as a child and
as an adult, and to be on that list is a bit overwhelming. Anyway, I will talk this evening about why
is life the way it is? Now I don’t know what you make of that question,
this is actually the subtitle of the book in English. I tried my subtitles out on people and I said
mew subtitles (?) will be why is life like it is, and she said it’s awful, I need a holiday! You can never quite predict how people will
react. The best title or subtitle of my books was
Power Sex Suicide: Mitochondria and the Meaning of Life. I had to find some way of trying to sex up
mitochondria, trying to get people to read a book about mitochondria. And it is strange because I have noticed it
is not cited as widely as I would wish or as other books are. I think people are a little bit ashamed of
citing a book with such a salacious title; it looks as if they are not spending their
time wisely. It is curious that people can only remember
one word from that title! The best review said they gave up smoking
after reading my book about oxygen and approached this book with trepidation. Anyway … This question for tonight, Why
is Life the Way It Is? Even in a scientific context it might be strange
you might think, life is anyway way. These are just animals, I’m told the blob
fish is real there. It seems just about my morphological shape
or form or way of life or way of being exists on the earth. How can that question make any kind of sense? If we look at a genetic tree which shows the
relationship with different animals, we are here, you might be able to read that – it
looks again as if all the genetic space has been explored thoroughly by the animals that
exist already. We can go broader than that; this is the entire
tree and so we include plants up here and animals are over there, protists, single-celled
organisms, fungi here and bacteria and archaea. This is not a tree of life. It makes me think of Magritte who said this
is not a pipe, which must irritate some people. I read this quote that he says, well, can
you stuff this pipe, and no it is merely a representation of a pipe. What we need to understand about the tree
of life is that this is just a representation. But it goes beyond the problem with the representation. The representation, it looks as if all of
this space is completely full, as if there was almost nothing left to explore and that
is an issue with the presentation of it. But it is also a tree of a single gene. And if you were to construct a similar tree
from a different gene you would get a different tree. The branches would be in different places
and so it is the tree of a gene, and if you try to do a tree of life and you construct
it from all the genes, you get a very different picture. I will come on to some of that. The other issue with this tree is that the
bacteria and the archaea down here look trivial; it looks as if there aren’t really any and
they are not very important and they are down at the bottom of the tree. It is a very misleading impression and again
you can understand if what we are really interested in are the animals up here and that is what
we have put the focus on, but as a representation it leaves something to be decided. This is going back now 20 years; this is an
equivalent tree using the same gene with a lot more perspective. It raises some really interesting questions. This is known as the three domains tree of
life. It was discovered by Carl Woese, who looks
rather like James Dean in Rebel Without a Cause, and he pointed this out in 1978, he
discovered this group had a look a lot like bacteria called the archaea. Nobody really had much of an inkling they
existed at the time, he came up with a tree, this was 1990, showing tremendous variation
within the archaea. The lengths of these branches give an indication
of the amount of genetic variation within each group. So the bacteria are over here, the archaea
over here and animal, plants and fungi were constrained to this small corner of the tree,
and other Copernican pushing the humans over to a corner and it feels uncomfortable. As soon as you look at this tree, it begs
two questions – and this is one theme that I would like to try to bring out tonight from
this evening’s lecture – that science is not really a collection of dusty facts at all,
it is a way of seeing the world, it is a way of testing those questions and trying to understand
how the world might work. And the kind of questions that we ask about
this are very simple, they are almost childlike questions, but it is easy to miss them. So why is it that these two groups have got
so much genetic variation and yet remain so simple? In terms of their morphology they haven’t
changed very much, there is nothing like Carl Woese woes built from bacterial cells, it
simply doesn’t exist. What was happening down this branch of the
tree of life that wasn’t happening over here? You can tell just from looking at that that
it was not really anything specifically to do with genes because there is plenty of genetic
variation there, it just didn’t lead to morphologically complexity. These are simple childlike questions but hit
you in the face as soon as you look at it. They don’t hit new the face at all from this. So again it comes down to the representation. So there have been, what would happen, I suppose
the question here is what would happen if you were to wind back the clock, if you were
to come all the way back to the origin of life and let the clock play forward again,
would we end up with something like that or something quite different? And there is no agreement, this is another
theme from science that I would like to get across. There can be tremendous intellectual arguments
about the meaning of things. This is a very good example. On the left-hand side as you are looking at
it we have Monday Jacques Monod wrote a bleak book that we were alone in an empty
universe and it was really a French existential philosophical life. Steven Jay Gould rolled back the time and
then played it forward and say what would we get human beings, vertebrates, what kind
of animals would we get. His view and it was a view is you would get
something very different to what we had. The evolution that has taken place is contingent
on the circumstances. You have a meteorite that wipes out the dinosaurs
and that gives the mammals a chance to get hold and that is all it is. We have Christian de Duve and Simon Conway-Morris
one of the subjects of Steven Jay Gould’s book and they both think far more in terms
of convergent evolution. The structural importance that if you want
to fly you need to have something like wings otherwise you will never get airborne. And so there are engineering principles that
force life down particular avenues. They see those avenues as being the most important. So these are different perceptions, but it
is important because you can say that it is simply counter factualism but the question
is can we predict anything about why life ended up this way rather than this way. Can you imagine what life might look like
in the universe, what kind of principles do we have to allow us get at those questions? These books written by these four are a wonderful
way of exploring the problem and laying out hypothesis, but the key things from a scientific
point of view is most of those are testable in one way or another, it depends on your
approach to the question. Here is how I see it. This is an indication of what’s happened to
bacteria over four billion years and they have been flatlining! They ended up with, you know, about the same
degree of morphological complexity. We can see bacteria and archaea in the fossil
record from 3.5 billion years ago and they look a lot like that. They look like modern groups we see today. So what have they been doing? In their biochemistry, in their molecular
machines, they are fantastic, but in terms of their morphological complexity they are
surprisingly limited. What was going on, and why is it then that
complex life, everything really that we can see, has a common ancestry. It appeared once after about two billion years
of evolution and all of this amazing array of different life forms are closely related
and share a common ancestor that arose around there. It is another way of looking at the tree of
life. It is a very different one. Something abrupt happened, something odd happened
and we don’t know what it was. I say we don’t know, that doesn’t mean to
say we don’t have ideas, we have plenty of ideas, the question is how do you know which
one is correct? What forces constrain the evolution of bacteria,
why didn’t they become large and complex, why not bacterial humans? How was it that the complex cells escaped,
the eukaryotic cells, I will talk more about them. Will these forces be similar on other planets? Could we guess what aliens look like, what
kind of constraints from first principles would apply to them. If we are going to ask this question, it is
really what is life? How do we think about it? This is Erwin Schrödinger who wrote a famous
book on that theme in 1943, I think. There were two famous ideas that emerged from
this book, one of them was the idea that genes are a code script. And that was the first time anybody had used
the word “code-script” or really thought in terms of information in biology. And he was absolutely correct. He talked – this was before DNA had been discovered
– he was a direct inspiration to Watson and Crick and many others. The second theme of the book was how life
maintains its organisation over time. Why don’t we just fall to pieces as entropy
would like us? He talked about negative entropy. He talked about
a footnote and said if I was catering for physicists alone I would have let the discussion
turn on free energy instead. I would say to put all of that into more modern
terms he says something like life is the harnessing of chemical energy in such a way that the
energy-harnessing device makes a copy of itself. That is certainly how I would see he’s linking
the two key themes of biology, information and energy, together. How do we generate energy, for want of a better
phrase? Well, these are our mitochondria, the powerhouses
of cells. So these are membranes inside and this is
where respiration is working at the level of oxygen and food reacting together to produce
the energy. There are in all of our cells we have in the
order of several thousand mitochondrias, hundreds to thousands of mitochondria. If you were to unravel all these membranes
here and lay them out you would have about four football pitches worth of membrane as
a surface area where respiration is going on. What is happening, and I’m not going to get
into any technical details, but effectively what we are doing is we are stripping electrons
from food as we’re respiring. These are giant molecular complexions, so
we are stripping electrons from food and passing them down this what is called a respiratory
chain to oxygen. It is a current of electrons. As simple as that, that current of electrons
that is pouring the protons across the membrane. We have a reservoir of protons on this side. Here we have the ATP synthase; this is driving
energy production and a turbine in the membrane. ATP is the energy currency that drives absolutely
everything in our cells. These blobs that I’m showing you. The level of understanding required to understand
how these work, I just want to give an indication. So Sir John Walker won the Nobel Prize in
1997 for the structure of the ATP synthase. The turbine in the membrane. This is Sir John’s own web page, this was
the state of knowledge in 1994; by the year 2000, he knew a little more. No structural information on the main part
of the main brain, this is only over 30 years this information has gradually been pieced
together. This is another key aspect of science, the
time it takes, it takes decades to get at these. It means determination and drive on the part
of the individuals and funding for those individuals over those kinds of periods of time to go
from a partial understanding of how something works to an extraordinarily detailed understanding
of how it works. We need to know that, but we also need to
conceptualise what does it actually mean, and the easiest conceptualisation for me is
a hydroelectric dam, this is very equivalent to what I have been showing you the water
equivalent to the protons. The turbine in the dam itself is equivalent
to the ATP synthase. This is how respiration works at the level
of cells. This idea was shocking, it goes back to 1961
with Peter Mitchell. This is in 1947 with Jennifer Moyle in Cambridge
at the time. He put this idea forward in 1961 that respiration
works by pumping protons across a membrane and he called it coupling. It was very mathematical and physical and
he tended to put a lot of people off, a lot of people got angry because they didn’t understand
quite what he was talking about. He had a knack of winding people up! And so it took a long time for these ideas
to catch on. There was what was known as the ox/phos wars. It was a period of particular acrimony where
people shouted at each other in conferences and so on. It turned out another finding of science that
pretty much all of them were correct in one way or another. But Mitchell himself was the person who conceptualised
the whole thing. He thought the ATP synthase would not work
as it does as a motor and physically combining phosphate on to ATP, he swore that was not
how it was going to work, but that is how it worked. The overall idea, I think Leslie Orgel captured
it nicely, he said not since Darwin has biology come up with an idea that is counterintuitive
of those of Einstein, Heisenberg and Schrödinger. I think people until then talked about chemistry
and molecules interacting with each other, the idea that there was a structural intermediary
of a proton’s difference across a membrane was shocking. Now Mitchell himself obviously saw the big
picture from the very beginning. This is from a conference in 1957 in Moscow
where just about anybody who was anybody was at the time. JD Burnell was there, all the communists were
there! Mitchell gave a talk at the same meeting. He said he cannot consider the organism without
its environment; from a formal point of view the two may be regarded as equivalent phases
between which dynamic contact is maintained by the membranes that separate and link them. He’s really dissolving the environment, the
outside world, and the inside of the cell. It is a novel way of seeing things. I think this is important and has been largely
overlooked. Mitchell himself, that is 1946, here is from
around the time he won the Nobel Prize and I’m very struck that his hairstyle hasn’t
changed at all in those 30 or 40 years. He looks exactly the same, just a bit older! So there is a big question about that though,
because this is a very complex way of structuring energy conservation. Why would you have a membrane? Why have this intermediary? Why should it work that way and how could
it have evolved in the first place; it is inherently complex. The fact is it is used by all cells. It is as universally conserved across all
of life as the genetic code itself. It is a shocking statement really that, but
this is just used by pretty much everything. So you would think that it goes right back
to very close to the beginning. So how on earth could it have evolved in the
first place? We can get some clues from the cells that
are the simplest they wills so methanogens and archaea, and acetogens, bacteria. They live between carbon dioxide and the hydrogen
gas. They get all they need from that reaction
alone. They need nitrogens and all that, but with
growth and the energy and carbon comes from this reaction. It is called a free lunch that you are paid
to eat. But one thing I want to bring your attention
to here: it is not easy to get hydrogen and CO2 to react, if we could do that we could
solve global warming, because we could strip CO2 out of the atmosphere. And we could solve the energy security because
we can produce synthetic gasoline. So there must be lots of people in secret
labs around the world figuring out how this goes on and they won’t publish it, so I don’t
know. I have to bring my own ideas to the problem. And I’m a biologist and I see what these cells
are doing. Over the last 20 years or so we now have a
much better idea of what these cells are doing. One thing that they need is a proton gradient
across a membrane and they can’t grow without that. If you look at roughly what’s going on – don’t
be intimidated by this – this is an energy map, if you like, if it goes uphill you have
to put energy in as a barrier, this doesn’t want to happen spontaneously. If it is going downhill it will happen spontaneously. You start with CO2 and react it with hydrogen,
the first couple of steps to get to this, this is formaldehyde, it is uphill, you have
to put a lot of energy in to get it to react. That is why it is not easy to do or economically
feasible to make synthetic gasoline from CO2 and hydrogen. What do the methanogens do? They reduce the barrier to make?? it happen,
and then it happens very quickly, they get all the energy from lowering the barrier with
the proton gradient. That points to me to a particular environment
on earth where life might have got going. These are alkaline hydrothermal vents, they
were discovered in the year 2000, relatively recently by Deborah Kelley who was the captain
of the submersible. They were discovered by a PhD student who
was on the trip as well. These are about 15-20kms off the axis of the
mid-Atlantic ridge. So there is nothing interesting there. Everybody knows that, so they were just getting
on writing their emails or whatever they were doing and the PhD student was the only one
who was looking out of the window and said hey, wow, what’s that! It turned out to be an entirely novel hydrothermal
system. Nobody had seen anything quite like this before. People predicted it might exist and nobody
had seen anything like it. It is not a black smoker, you don’t see the
black smoke welling out of these things. It was called Lost City in part, it was on
the Atlantis area and it was linked to it. It looks almost abandoned and there is a strange
empty feel to the vent system. This really is again another theme of science. This is a serendipitous discovery, it is really
exploration, and I can’t overemphasise the importance of just exploration in science. Finding out things about the world; looking
at what there is to see. So these vents I mentioned had been predicted,
they had been predicted by this guy, Mike Russell, about ten years earlier. His ideas at the time were really considered
a little bit leftfield probably for most people, in some respects they still are. But the discovery of this vent system which
conformed so closely to the kind of properties that he said they should have really made
him famous overnight. This was an article by Nature, the leading
science magazine. They dressed him up as Erasmus and called
him Nascence Man and linked him to the Renaissance and dressed him up as Erasmus. I have noticed how sartorial standards have
dropped. I’m trying to stop the rot and I don’t wear
a tie often. What Mike Russell argued is that these vents,
if you look inside them, there isn’t a central chimney, you just have this kind of porous
rock, it is like a sponge, a mineralised sponge, and the hydrothermal fluids percolate through
the sponge. You have high amounts of hydrogen and carbon
dioxide, and the proton gradient, the oceans four million years ago were acid and this
is very alkaline, today they are mildly alkaline but far less than the fluids. He said this is very equivalent to cells as
we know them. This is what they look like if you go down
to the level of inside one, so this is perhaps a few micrometres across, much less than a
millimetre. We have a relatively thick barrier separating
the ocean waters and I’m thinking here deep inside the vent. The ocean and hydrothermal fluids come in. On one side it is acidic and the other side
alkaline. This is roughly what cells look like, so cells
are pumping protons out all the time. On the outside they are relatively acidic
and inside relatively alkaline. The difference across the barrier is three
PH units, give or take in both cases, and in both cases it is acid on the outside. It is very analogous, it is inspiringly so,
but there is no reason at all to think it should be any more an analogous. The question is could it be, is there an experiment
to do to test if it may work? There are simple experiments we have started
doing in the lab and we can produce these hydrothermal structures, containing the minerals
and the question is can we use the structure and the difference in ph. across the barrier
to drive the formation of organic matter? It is very early days but I will show you
this. This is formaldehyde, and it has different
energy levels. It does look as if that structure might promote
this reaction between hydrogen and CO2. What I want to draw your attention to about
the vents is they are formed by a chemical reaction between rocks, the kind of rocks
that you find in the oceanic crust, magnesium and water, it will percolate down into the
crust to departments of five or six kilometres. This is the ocean above and they react with
the rock and it becomes changed and it is converted from olivine into pentonite. We have warm fluids bubbling back up, and
when they are in contact with the ocean waters they can precipitate these amazing vent systems,
up to 60ms tall. The only requirements are rock and water. So you would expect to see these kinds of
vents on any wet rocky planet. There is even some evidence from our own Solar
System, so this is Enceladus, and on Enceladus you see these geisers periodically, and from
the ions dissolved in those you can work out the Ph, and that seems to be 11, there are
few processes that will give a Ph to oceans of 11. On Mars there are perhaps traces of methane,
and it is either coming from life, which is difficult to believe, or coming from this
geological process, reacting, traces of water down in the rocks with the rocks themselves. And of course Europa is another place to look
and again it has massive oceans and there are some signs that some reaction is going
on. The real key point from all of this first
half of the talk is that wet rocky planets will form this type of vent, bubbling with
hydrogen gas, it should happen on potentially tens of billions of exo-planets across the
Milky Way alone. They should have natural proton gradient,
and those natural proton gradients should drive this difficult reaction between hydrogen
and CO2, and it begins to make sense for this broad shape, why is it the simplest cells
are using proton gradient, and why did it spread to everything else? This is a way of seeing it that makes some
kind of sense and again it might not be true but at least we can try to test it. If it is true then life elsewhere should face
rather similar constraints. We can get at this question, why was it that
the bacteria have been flatlining for four billion years? Why did life get stuck in a rut and would
it be the same reason elsewhere, and would it be the same requirement for proton gradient? It is what I like to think that John Maynard
Smith would have called an evolutionary scandal! John Maynard Smith was a great evolutionary
biologist, one of the doyennes of evolutionary biology of the 21st century and at UCL as
I am and I’m proud of that. He worked largely on the evolution of sex
which was very much an evolutionary scandal, but I think he saw this problem in similar
terms as well. The problem is that all complex life is composed
of this one cell type, the eukaryotic cell, which arose only once in the entire four billion
years of evolution. Maybe they arose at other times but we have
not seen any other sign of them. Nobody has ever found one. So to the best that we know they arose once. And all eukaryotic share kinds of traits,
we are all sexual, for example. And bacteria don’t seem to evolve any of those
traits at the morphological way in the same way. The scandal is if all the traits form step
by step by standard natural selection and each small step offers an advantage in the
conventional way, why don’t we see any of them arising in bacteria for similar reasons? It is not obvious. I’m not criticising natural selection at all. The question is what are the constraints that
are operating on natural selection and is energy one of them? Just to give you a sense of the problem here:
eyes, for example, they are often dismissed by creationists as being what use is half
an eye, and you have the feeling that natural selection is laughing at them because these
are all different types of eye. This, for example, this is an eyeless shrimp. It doesn’t have eyes at all but these photosensitive
strips on its back. This is a pond scrum, it is a single-cell
algae, this is an eye spot. This is another remarkable single-cell protist
and this is the retina here, all inside the single cell, it is made of chloroplast, usually
used from photosynthesis and it has cobbled together this now. And the powerhouses are used as part of the
cornea for this eye. There are all different types of eye. This is scallops, astonishing things. In animals they can trace a common ancestor
which is a light-sensitive spot on some kind of an early worm. And there are some regulatory genes in common,
but those regulatory genes independently recruited all the re- of the genes to evolve a complex
morphological eye independently. So the eye of an octopus here is very similar
to our own eye in its overall structure but it is completely originally evolved. It doesn’t share a common ancestor. This is convergent evolution. So what was going on then? Down here. Why was it that all of these bacteria in archaea
in all the billions of years in all the variation, why couldn’t they come up with something like
half an eye or half of a nucleus or phage cytosis and all the complex things that cells
do and they don’t do? What was happening down here that wasn’t happening
over there? I like to think of this as the black hole
at the heart of biology. It is not just at the level of multi-cellular
organisms, it is also the cells themselves. This is planctomycete, a relatively complex
bacterium; it has a structure you might be able to make out. It is compartmentalised, called a little bit
like a nucleus, not that similar but it has a relatively complex structure. It is roughly to scale which is why you can’t
see it very well, this is the pond scum I mentioned a moment ago. You don’t need to know what any of this is
to realise it is on a completely different scale to the bacteria with a lot going on,
this is the chloroplasts and the nucleus, we don’t need to know that to appreciate there
is a big void in complexity even at the level of single cells. What was going on? The other thing I want to call your attention
to is within the eukaryotes themselves, the level of complexity is strikingly similar
in different types of cell. This is paramecium and this is a par Cretic
acinar cell, they look similar, and I ask my students in the first year when they start
how many genes do they think cells does paramecium have, they range from ten to a few thousand,
the actual answer is 40,000, that is twice as many as we have. So the level of complexity in terms of protein-coding
genes in single-celled pond scrum is quite striking. I’m making fun of the students but I should
make fun of the professors as well! When the human genome project was just coming
to fruition in around about 1999, there was a sweepstake to try to guess the number of
genes that there would be. The average number that people guessed was
80-100,000. And of course now we know the answer was 20,000. And I have to say on behalf of evolutionary
biologists that the evolutionary biologists in the late 1960s-70s on the basis of mutation
rates had demonstrated that the human genome could not have more than 30,000 genes. Unfortunately, the scientists who were working
on unravelling the genome itself didn’t know that literature. That is another point about science, it is
very difficult to keep abreast of the very wide literature and have an idea if you are
in one field of what people have been doing in another field. It is very, very difficult to do that. Another thing we all have in common, all eukaryotic
are sexual, sexual in the sense that cells fuse together and the nucleus fuses together
and we don’t see that at all in bacteria. There are quite a few eukaryotic cells that
appeared not to be sexual. This is amoeba, for example, and until 2011,
so this is Dan Lahr here, I imagine he’s out looking for amoeba in the woods! But we knew they had some genes that were
linked with sex but they had never been caught in flagrante, and Dan finally caught them. This is amoeba having sex! I must say I was a bit disappointed! I don’t know quite what I imagined I thought
they would be bristling and exciting amoeba but it isn’t how it looks! The key point I have to get to the argument
here is that all eukaryotic cells had or have mitochondria. So this link with energy can explain why it
is that all complex cells only arose once. So all of these cells do not have mitochondria,
they lost them. And it is another illustration of science,
it was a very good hypothesis from 30 years ago saying perhaps these were primitive and
they never had them. Testing that hypothesis shows it was wrong. The importance of being wrong in science is
vital as well because we know an awful lot more about these cells. It turned out that they did have mitochondria
once upon a time. Lynn Margulis showed really in 1957, 50 years
ago this year, that mitochondria derived from bacteria. This is Lynn Margulis. She married Carl Sagan, it is an anti-celebrity
marriage, I’m sure everyone knows Carl Sagan, but Lynn Margulis was a celebrated evolutionary
biologists, celebrated and worried about because some of her ideas, the ideas to do with mitochondria
and chloroplasts being derived by bacteria were true, other of her ideas turned out not
to be true. Another theme from science is she persisted
with the ideas and the ones that were true after 20 or 30 years everybody accepted them
to be true, but it required a real dedication on the part of an individual who is being
tormented. There were papers published dismissing what
she was saying, but it turns out she was right about a lot of important factors. She was asked during the end of her life,
“Don’t you get tired of being called controversial all the time?”She responded to say, “I’m
not controversial, I’m just right!” So this was the derivation of the host cell. Less than a month ago we now know the host
cell was an archaea. Related to the lokiarchaeota. Near Loki’s castle. A year ago there was a paper showing the host
cell was closely related to the lokiarchaeota, which were dredged up from down there. We have never seen the cells, we have a genome
sequence; this is environmental meta-genome reconstruction. More systematically across the world, a couple
of weeks ago they have come across? one another paper saying this is a super thing with different
groups. The lokiarchaeota are here, we have the thorarchaeota
and the thing is going there. This is how the tree of life now looks. This comes from a friend of mine, Bill Martin,
one of the most brilliant scientists of his generation and not always appreciated because
he can be a bit prickly. This was his conception in 1998 that we have
separate origins from a vent, from a hydrothermal vent, the system I have been talking about,
independent origins from a common ancestor from that vent of the bacteria and the archaea,
and the eukaryotic are a single event, an endosymbiosis. It started something like this is the only
example we know of bacteria living inside a bacterial cell. The key point about it is, the reason it matters
is that you have a population of cells in there and when you have population of cells
what bacteria do, if they are just growing, you can imagine this is a population of bacteria
and this yellow cell here loses, it has a mutation, it is wiped out a gene that it doesn’t
need any more. It has a slightly smaller genome and it grows
slightly faster. Over time it comes to dominate. By here, pretty much all the cells in that
population have lost that gene because they don’t need it right now. But then the conditions change and they do
need it again and they pick it up, from somewhere in the environment by a process called lateral
gene transfer and before you know it you are back where you were. What happens here if you have the same population
of bacteria inside a cell they lose that gene and they never need it again. So they just waste away, getting smaller and
smaller; it is a genomic streamlining going on. We know plenty of examples of this type of
thing going on. Typhus is an example of it. This is Napoleon’s retreat from Moscow where
the army was almost obliterated by typhus. It is caused by a bacterium, an intracellular
bacterium, this is Rickettsia, inviting a cell here the key thing about Rickettsia is
it has a tiny genome a fifth of the size of most bacterial genomes, it is one in size. This is the free living bacteria coming across
here 12 now megabases and here are the intracellular ones, the parasites and the symbionts, one
megabase, most of the work is done by Ryan Gregory, you see a striking difference if
you are living inside another cell you throw away everything you don’t need and you become
small and dedicated to a particular way of life. And that’s what happened to the mitochondria,
the mitochondria started out as bacteria and they ended up with a genome of their own. Very, very tiny genome, 99% of their genes
have gone. It is a really interesting question, why did
they retain that 1%? And the answer, it comes from John Allen here
in the audience, and this is another wonderful idea that John put forward first in 1995 and
it is still not generally accepted though it should be! I don’t have time to go into details but effectively
all of these mitochondria here have their own genes which they use for controlling respiration
locally. So the membrane potential on these, the actual
electrical charge across those is about 150mili volts, if you were to shrink yourself down
to the size of a molecule that would be equivalent to being a field strength of 30 million volts
per metre which is equivalent a bolt of lightning. The charge on the membranes enormous, they
need that to deal with that charge. Just for the last couple of minutes. What is actually going on? This is the situation. If we see giant bacteria, they have thousands
upon thousands of copies of their complete genome. So it is a thing called explosive polyploid. They need it to control respiratory, in the
same way that eukaryotic do. This is a eukaryotic, in red, the mitochondria
and the green dots are the mitochondrial DNA, they have the tiny genomes supporting the
big genome. We have a symmetry where all the genomes are
the same size and shape in bacteria, they expand up and copy and copy and copy and there
is no evolution going on they all remain the same. But here over time these genomes will become
tiny and they can support then energetically that massive nuclear genome. Why did complex life only arise once? It required at the very beginning a singular
endosymbiosis it is rare we only know one example. There are no known surviving intermediates
of this process, they have to find a way of syncing up their lifestyles. There was that quote about hell being other
people and this is what is going on here. This is the equivalent to the common ancestor,
this is the black hole at the heart of biology and it is difficult to get at how it happened. Another important take-home message is when
we are trying to understand what is going wrong in diseases and things, it is important
to know how all the parts of a cell relate to each other, how do they work, how do they
function, how do they evolve to be that way? If we can’t understand that, it is difficult
to understand how they go wrong. At the moment we don’t really have a good
idea of exactly how they all evolved in the first place. As I said earlier we have ideas but we don’t
know which is the right answer. So I have said that life arose only once,
complex life and it was very rare. And that may depress some of you. And so I want to give you a hope and cut you
a little slack. This was discovered in 2011 and it is not
clear at all what it is, which is another lovely thing about science. We don’t know what it is. The lokiarchaeota, we have a genome but we
don’t know what the cell looks like, so we try to piece it together from the genes. In this case we know what the cell looks like,
it is this, but we don’t have a genome so we don’t really know what it is. Now this is not a normal cell. It has got what looks like a nucleus here,
quite large, it has some things that look a bit like hydrogenosomes but they could be
bacteria. It has membrane and cell wall. It looks like a fungus of some sort, but when
you look more closely you realise that the nuclear membrane, it is a single membrane,
it should be a double membrane, it is a single membrane, that is odd. All of this dappling here, these are ribosomes
but outside the nucleus which is weird, this is fusing the membrane there are a lot of
things wrong with the cell. It might be all part of the preparation, we
don’t know. It might be that it is somehow recapitulating,
that we have the cells within the cell and it has become larger, these are normal-sized
bacteria here, it is becoming large and developing a nucleus, it is recapitulating eukaryotic
evolution, the downside is they have been trawling it trench off the coast of Japan
for the last 15 years and only found one like that and they have never found another one. So it is very rare and perhaps complex life
has arisen on multiple occasions but went extinct before it got very far. I want to finish with this. I’m sure some of you will recognise this as
the pale blue dot which is there, that is the earth and this was vow Voyager 1 in 1990
when it was beginning to leave the Solar System and Karl Sagan managed to persuade them to
turn around and take a picture of the earth. Bands are light-scattering artefacts and not
true at all. And Karl with his characteristic eloquence
said that everything which we know about, everybody we have ever loved, and everybody
we have cared for, everybody who ever lived, all the civilisations and the empires and
the tyrants and the religions and everything that’s happened on this planet from the very
beginning happened on that pale blue dot. The thing that strikes me about it as well
though is how inscrutable it is. How could we know anything really about that? And science itself, well the word is inscrutable,
it is almost impossible to know anything about all of this and yet we do. We know about the rules and atoms and quarks
and membranes and strings, and we know the other side about black holes and we know about
the structure themselves and the proteins that make them up and how they work, this
is from the process of science over hundreds of years, finding ways of asking probing questions,
it works a little bit like natural selection in the sense that there are always competing
hypothesis and ways of seeing a question, it is the testing of those questions just
as natural selection distinguishes between different versions, some of which work better
than others. In science there is a ratchet like way of
improving our knowledge over time and beginning to get at some answers. A lot of science is now in dusty textbooks
because it was established a long time ago. Where science is really at in the process
of discovery and trying to understand new things about the world. That process is inevitably about competing
hypothesis and arguments and different ways of seeing the world, that is how it needs
to be but it is also a dangerous way of presentation I think in the modern world where experts
with are dismissed as being meaningless. We have to find a way as society of somehow
getting people to think more clearly about what science is as a way of thinking about
the world and questioning the world and getting at inscrutable information. This is one of the reasons why I think books
are valuable, why any form of public engagement is valuable. It is vital, I think, if we want to keep the
whole western way of life alive, which is based on this scientific understanding of
the world, we have to find a way of making, of getting everybody to appreciate the process
that is going on and when they see two scientists arranging with each other they will appreciate
that they are arranging about details and they are arranging about how to move forward,
they are not arranging necessarily about what we know from the past. I think that is a key message to end with. Thank you all very much. [Applause]. NICK: I have overrun slightly I hope we have
time for questions. ADRIAN: Nick has agreed to take ten minutes
or so of questions. Could I ask you please to use the microphones
if you want to ask a question. And if you can please stand up. So who wants to ask a question? We have one down here on the left? FLOOR: Thank you very much. I just wondered about the chloroplast. I always understood that chloroplasts were
another endosymbiont, an extra one. Can you clarify that? NICK: Yes they are, it was not a singular
event that gave rise to complexity. The acquisition of mitochondria gave rise
to all eukaryotic cells, every one of them, and then in one group later on they acquired
a Sino-bacteria that went on to become a chloroplast, it didn’t affect the entire direction, it
affected everything in the sense that it a0 load photosynthesis to take off in a different
way and changed the way the world went, but in a conceptual sense it doesn’t alter the
pact, it was a singular endosymbiosis at the beginning. FLOOR: I wanted to ask if you were aware of
anybody mixing together archaea and bacteria under a variety of conditions to see if you
can observe a bacterium getting into an archaea? Has anyone attempted that or is it regarded
as so improbable? NICK: I would love to try do it. It is not an easy experiment to get funding
for and you can’t inject one inside the other. You could do that but it would fail because
you need to have a way of making a living inside another cell and the ideas are that
there would be lots of gene transfers going on and you would need to set that up in the
lab. I have met several people who have told me
that they are doing exactly that and the strange thing is I have never seen any of them since! FLOOR: Is it fair to conclude that because
it took so long for eukaryotic cells to derive that if there is more life in the universe
it is more pro-eukaryotic and we don’t need to worry about ET! FLOOR: I was wondering if some cells have
developed in a way that they don’t need mitochondria anymore? Is it possible for cells to evolve in a way
that they take the shortcut from the beginning? NICK: I would say no, it is not possible. And that’s a hypothesis that may turn out
to be someone (somehow?) wrong if someone shows a complex cell tomorrow that never had
mitochondria. We know of a lot of cells that don’t have
mitochondria, it is perfectly possible to be complex and not have mitochondria. The question is really is it possible to become
complex in the first place without having mitochondria. And the energy difference of having mitochondria
makes is (it?) actually immense. I didn’t really mention this, it is about
100,000-fold against in the energy availability in the gene that eukaryotic cells have above
bacteria. It allows you to just ramp up on a massive
scale and have more for photosynthesis to have more genes and bad genes. It doesn’t affect you very much because you
have bucketloads of energy sloshes around and you can deal with it. Once you have got all of that, and most of
these cells who have lost their mitochondria are phagocyte, once you are that can you go
around and engulf other cells, which means you may not get much energy out of eating
them but can you eat more of them and you will be all right. Whereas if you tried to do that as a bacterium,
there are no bacterial phagocyte. The whole process is so costly, that is the
barrier. The bacterial cells that just ferment, they
exist as well and are tiny. They can’t extract hardly anything, they can’t
eat other cells they have to use the resources of the environment. They have the smallest genomes of any known
bacterial cells. ADRIAN: One last question here in the middle. FLOOR: Life has been around for four billion
years, but eukaryotic cells only around about two billion years. Fusion event took place not long after the
great oxidation event, therefore once you had oxygen in the atmosphere that sort of
fusion essential is possibly more likely? NICK: That is what Lynn Margulis’ original
thought. FLOOR: It could be a little more likely from
what you are saying? NICK: That sounds reasonable on the face of
it. The problem with it is we don’t see multiple,
that is what you would expect to see, once you have oxygen you would expect to see for
example cyano bacteria might evolve into the plants, and they are preadaptive to that lifestyle,
why not go on and pick up another cell if they need one if it is easier to do with oxygen. Why not fungi, why are they not derived from
bacteria a similar lifestyle? Why don’t animals arise from phagocytic bacteria
or predatory bacteria? What that theory pro-directs multiple origins
like a bottleneck, we should see multiple origins, not tens or hundreds but two, three
or four of separate origins of complex life, but that is not what we do see. It is not at all clear when the eukaryotic
arose or whether it was linked to the period after the oxidation event. Also, over the last ten years, we see oxidation
then but not much oxygen. Most of that gets consumed by oxidising the
rocks themselves and that is why we see the red beds and so on. But in the oceans there is very little oxygen
for another billion years, really until the time of the Cumbrian explosion and we see
animals abruptly, and that was probably linked to oxygen. ADRIAN: I think we better stop the questions
there. We now come to the formal presentation. So Nick it is my pleasure to present to you
the scroll. And also the medal. And finally the cheque! [Applause] Wonderful congratulations. [Applause]
So, ladies and gentlemen, a right of (kind of?) function is due to take place in this
lecture hall shortly. In order for our staff to prepare the hall,
we would be very grateful if you could make your way to the exit as quickly as possible. Unfortunately Dr Lane will not be able to
remain to answer any further questions. Guests attending the private function should
make their way to the City of London II room which will be on your left as you exit there. Thank you very much for coming. I hope you have enjoyed the evening. Thank you.

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