The evolutionary logic of survival and death, in 54 minutes

How can all the diversity and sort of seeming order that's out there in the world

emerge from a process dependent upon chance? It kind of works like a staircase

Chance invents and natural selection propagates that chance invention. Our immune system works on the very same principles of mutation and selection

as evolution at large does in the big world. Cancer is truly an evolutionary disease

meaning that it is a disease that results from the exact same evolutionary process we're describing

So while Darwin's is the most famous figure associated with the theory of evolution

Alfred Russell Wallace played a key part. And in their day, this was referred to as the Darwin-Wallace theory

I'm Sean B. Carroll, evolutionary biologist and author of several books, including my most recent series of fortunate events

Chance and the Making of Planet, Life, and You. Chapter 1. How Life Works, The Staircase of Evolution

So evolution, what it really means is change over time. So we want to know how that change occurs over time

And there's two dimensions to this process. And it kind of works like a staircase

And one process is mutation. And that's the rise in the staircase

those occur by chance. If mutation didn't happen, all things would be identical. So you need mutation

to make individuals different from one another. Those mutations are genetic changes, changes in

their DNA. If by chance that changes a property that favors reproduction, survival of the individuals

it will spread. And that's the selection process. And that's sort of the run in the staircase

chance invents and natural selection propagates that chance invention. And once that process has

happened, new mutations can then be added on top of that, maybe even changing the character a little

bit further. And that's another rise in the staircase. And if that's working better, that's

going to spread. And so it's the cumulative set of mutations and the cumulative process of selection

that takes us up that staircase. So that staircase could have goodness knows how many stairs

but it has to go through this stepwise process of individual mutations arising

sweeping through the population, new ones arising, sweeping through the populations. It doesn't go from the base of the stairs to the top of the stairs in one jump

And this is hard for people to get their heads around because they may think about that first step. And it's sort of hard to imagine, you know, how do you get something as complicated

you know, as individual organs like an eye or a wing of a bird or things like that

But time, immense time, the speed with which some new adaptation spreads through a population

depends upon the magnitude of the advantage it conveys. If it's about a 3% advantage, meaning that about 103 individuals survive for every 100

that don't have it, well, that will take about 1,000 generations to spread through the population

Now, I'm saying generations because it depends upon the generation time of the creature. So if the generation time, for example, if humans is 25 years, it'll take 25,000 years

for that to spread through the human population. But if the generation time is 20 minutes, you can work it out

It'll take 20,000 minutes to spread through, which is much shorter. It's a matter of generations because its reproduction is a generation by generation process

It's really important to underscore that these mutations occur at random, without any consideration

of whether they're good or bad for the organism. It's the external conditions that are going to sort this out

So some things can be good for one creature and bad for another

So, for example, a color change might make a creature more invisible in some settings, more visible in another

Some mutation may make it better adapted to warmer climates, less well adapted to colder climates

So it depends on these external circumstances. So the mutations arise at random

Well, what about those external circumstances? Well, we'd say the abiotic conditions

whether the physical world that the creature is living in. Well, that's also generated a lot at random

Tectonic plates moving across the earth, you know, volcanism, all the things that shape the conditions of life

are often due to physical processes of the earth. Of all the many thousands and millions of things

that creatures have come up with, I have a few of my favorites that I think really exemplify this process of adaptation

And one of my favorite sets of creatures are some fish called ice fish. They live in the Southern Ocean around the Antarctic

And they live in water that is actually below the freezing temperature of fresh water

They're right around about 29 degrees Fahrenheit is the ocean around the Antarctic

And that's a challenging environment. So challenging, for example, that you may know that there's ice flows around there

And if little ice crystals just get into the bodies of these fish, they'll nucleate freezing

They'll freeze like fish sticks. So they need to have a mechanism that prevents them from freezing at that cold temperature

And what they've done is they've evolved antifreeze. Certain proteins in their bloodstream, made in very large quantities

suppress the ability of ice crystals to grow inside their bodies. And so they're able to

tolerate that sub-freezing water of the Antarctic. And other fish aren't. So what's happened over the

last 30 or 40 million years is that a lot of fish that once swam in those oceans, sharks and rays

and all that, they're all gone. They're extinct from those waters. We find them in more temperate

waters. But it's the ice fish and the antifreeze-bearing relatives that exploit those waters

And the ice fish have also come up with something that's incredibly nifty and shocked naturalists when they first discovered it

Which is, if you open, which any fish you know, slice it open

you're going to see red blood because that's something that animals with backbones have

and have had for almost 500 million years on this planet. But you slice open an ice fish, their blood is colorless

because they've gotten rid of red blood cells. So they don't even have a mechanism for carrying oxygen actively in their bloodstream like we do

They've ditched red blood cells. And the reason they've ditched red blood cells is at those low temperatures, it makes their

blood too viscous. And that's a disadvantage. To the ice fish, it was an advantage to get rid of red blood cells

To the rest of us, it's instantly fatal. So it's a good illustration of just how conditional these adaptations are, that to exploit the

resources of the Southern Ocean, you've got to make antifreeze and get rid of your red

blood cells, where the other parts of the world antifreeze would be irrelevant and your red blood

cells are necessary for every second of life. Let's talk about speciation. That process of

variations, helping to adapt, that's the process of adaptation. But speciation is the generation

of two species from one. What does that take for there to be two species to form

And we know, this is where the island biology of Wallace and Darwin help, is that they were seeing

species on different islands Well islands provide some isolation and that isolation means that those populations aren exchanging genes Over time each of those populations will

accumulate mutations that exist in one population and not the other, vice versa. Well, those can

become genetically distinct enough that if those things were ever to come back again in contact

They may not be compatible with one another, and they'll be species

So how long does that take? Well, it's been estimated for big animals like mammals and birds

that works out to roughly be about two million years. But two million years is still a long time

And you've probably heard, for example, that there's now very strong evidence

that Homo sapiens, our species, mated with Neanderthals, a distinct species. And what's really happened in the last few decades is that for biologists, that species barrier has become much more porous than we first thought it was

In the old days, in Darwin's days, species were characterized as really distinct things, and we didn't think there was any kind of shenanigans going on between them

But we now understand that it's a much more porous situation, that for some period of time, as populations are diverging, they can get back together

and things that we humans might call distinct species can often interbreed

Another common question or idea is that, you know, for example, if humans evolved from apes, why are apes still around

Well, the important thing is to understand that evolution is a splitting process. So the family trees keep splitting

So the human part of that tree has had now its own separate history from the ape part of that tree

We shared a common ancestor about 6 million years ago. But apes have gone on living as they do, for example, in the old world

And there's a great diversity of apes, of course, still here, baboons, orangutans, gorillas

chimpanzees, et cetera, while the human branch has gone on and has its own evolutionary trajectory

It's not that evolution is linear and that everything new replaces the old

It's a splitting process. And so that's why the tree of life has just split into enormous numbers of branches

from common ancestors. Two of our main records of evolution are the fossil record and the DNA

record. The DNA record is largely only accessible to us for living creatures and maybe some creatures

that have lived over the past million years. You know, do we have every brick? Do we have every

intermediate? No, because, you know, extinction takes away 99.9% of all species. So if there was

no extinction, we'd have a perfect record of evolution, right? We don't have the DNA record

of dinosaurs, for example, but we've got the fossil record of dinosaurs. So we use these two

records to sort of reconstruct the history of life. That allows us to reconstruct the evolution

of things that are fairly complex. Let's take something like a walking limb from a fish fin

This evolutionary process transpired over 20, 30 million years, about 380, 390 million years ago

To do that, we have to get fossils that represent the various stages of evolution and see how did

all the bones change so you went from a swimming fin to a walking limb. And the fossil record by now

is pretty darn good. Then we can go to creatures that have fins, fish, and we go to creatures like

amphibians that have limbs, and we can figure out how do those genetic programs work and where are

the differences. Now we don't have every detail sorted out, and that would be incredibly time

consuming and expensive to do. But we certainly have the general picture that we understand how

the bones changed in history, and we understand how the development program changed to generate

a limb in the place of a fin. And that's not something Darwin ever had. That's something that

we really only had for the last 20 to 25 years. So evolutionary science keeps building on this

huge foundation. And what we get is an ever more detailed and ever more confident record of what's

happened. But what's it no doubt is that this process, mutation and selection, mutation and

selection, is the universal going on in every population of every living thing every day

In fact, this process of mutation and selection seems so universal that we think it must have

played a vital role at the origin of life. And that anywhere where life exists in the universe

it's operating. So evolution is this vast and rich process. And we've been trying to understand it

for 160 years. And in the course of that, there's some misunderstanding in just how it's communicated

where I think there's some conflict between the terms we scientists use and sort of their

common understanding. And one of those is theory. We talk of scientific theories. Theory is much

higher in the hierarchy than, for example, a fact or just an observation. A theory is assembled from

lots and lots of facts and independent lines of evidence that sort of cohere. So a theory is

really sort of the top category of scientific idea. Of course, you know, in the street, theory

might mean that's my best guess, or that's just something that I'm conjecturing. The way we talk

about those kind of conjectures, we call those hypotheses. And then when hypotheses have been

rigorously tested, that's what can contribute to making a theory. So folks, when we speak of theory

think that we're still very tentative about, you know, the truth of evolution. That's not all the

case. The theory of evolution, which has grown enormously in the last 160 years, is a huge body

of observations, evidence, and facts that are consistent with one another, that come from

completely different sources of science. And that's what gives it its power. We, of course

wish that maybe that connotation of theory that's more of the everyday connotation would

be better understood. Chapter two, how our bodies work, the staircase of self-defense

Now, here's something about the staircase of evolution that's very little appreciated

It's going on in every one of our bodies every day. It's keeping us alive

And that's because our immune system works on the very same principles of mutation and selection

as evolution writ large does in the big world. Every day, we are exposed to all sorts of potential pathogens

Bacteria, viruses, fungi, parasites. We've got to fend these off. And by the time we're full-grown adults

there are actually more bacterial cells living on and in our bodies

than there are our own cells. Trillions and trillions of microbes. We've got to keep these in check

or, of course, will suffer and potentially die. And that's the job of our immune system

And our immune system operates on the very same principles as the staircase of evolution

It's a staircase of self-defense. And the most remarkable property of our immune system

is it seems to be able to recognize as foreign virtually anything that can come at us out of nature including entirely new pathogens that didn even exist in the human population And how do we do that Well it involves a process

based on mutation and selection. And the way this starts, I'll just describe it starting with a

single cell. So you have billions of cells, but these cells have different molecules on their

surface that when they are complementary to molecules on the surface of a pathogen

they're activated. They're engaged. And when engaged, they multiply very rapidly such that

over a period of about a week, one cell may become billions of cells and start to pump out

large quantities of chemical weapons known as antibodies that thwart that invader. These

billions of cells of our immune system are actually clones. Clones that are subtly distinct

from each other that have unique ability to recognize something else. Now that something else

could be any variety of things on an invading pathogen. But once they recognize that, that clone

gets amplified, can grow to be many, many, many cells in the course of a week or so

That first wave of defense is decent, but not optimized. There's actually a mechanism

to make those chemical weapons, the antibodies that cell makes, even more potent, even more deadly to essentially the invading pathogen

And that's because there's a specific genetic mechanism that mutates the antibody encoding genes

leaves the rest of the genes in the body alone. Just the antibody genes start undergoing a process called hypermutation

and therefore generating all sorts of antibody variants. and the antibody variants that recognize the pathogen better are selected for

So here we go. We're climbing the staircase. So this hypermutation process, you now select antibodies

And this can go through various cycles to make ever better and better antibodies

So we're really zeroing in on this particular pathogen. So late in immune response, say, for example, the second week you're recovering from a flu virus

your immune system is ever more potent, ever more powerful in defeating its enemy

because it's up that staircase. Eventually, a staircase sort of splits. And some cells are set aside, so it's called memory cells

They're there to be used when this pathogen is encountered again. Other cells continue to make the antibodies

Now, this is the marvelous thing. Y'all are familiar with a phenomenon where, for example, you don't get measles twice

you don't get chicken pox twice, etc. Why is this? Immunological memory

That even if 50, 60, whatever number of years ago, you might have been exposed to that virus

your immune system is still poised to attack it again if you're exposed again

so you don't even get the infection. This system is called adaptive immunity

much like the process of evolution of mutation and selection is adaptive

It really only exists in this form in animals with backbones, long-lived, generally larger animals

And you can see its utility because the longer your lifespan, the greater the chance you're going to re-encounter a particular pathogen

If you're a short-lived mayfly or something like this, You don't live long enough to see the same thing twice

There's not that kind of immunity. So lots of animals, including simpler things like worms and flies and all that, they have

what we call innate immunity. They have ways that sort of put barriers up against pathogens

But this adaptive immunity only exists in creatures with backbones, with vertebrates

And it's pretty elaborate in us, in mammals, animals with fur, et cetera

but it's pretty well developed even in things like fish and sharks. Inside our bodies, the time scale of this process is very, very fast

It's more like what we described with respect to microbes because it starts with cells and cells that can multiply pretty frequently

So a lot of evolution can take place in a short time. Most of us are sort of familiar that most infections don't knock us down for more than about a week

That's when our immune system eventually sort of catches up and overtakes the pathogen

So that gives you a sense of the timescale it takes to mount the response, expand that response to the point where it overwhelms the pathogen

Whereas out there in the world, sort of a battle between predator and prey or whatever, that may go on for hundreds of thousands of years before there's sort of a winner

Same process, much more rapid timescale in your body. How is it possible that we can recognize virtually anything that the world will throw at us

And fundamentally, one of the problems there is sort of a coding problem. how can one make all the different kinds of antibodies that could recognize all the different possible pathogens that, you know, a species might encounter

And the solution to that required understanding how antibody genes are encoded in DNA

something we weren't able to do until the 1970s or so. And what that's revealed is that we mix and match pieces of antibodies in a way that we can generate millions of combinations of antibodies

And it's now estimated that we may be able to make about 10 billion different antibodies

And you might go, well, that sounds sort of impressive, but okay. Well, here's the thing

In our entire genome, all of our DNA, we only have about 20,000 genes

So how do you make 10 billion antibodies when there's only 20,000 genes to begin with

And this is the brilliant trick of the immune system. It makes antibodies from short little gene segments that it mixes and matches in millions

if not billions, of combinations. So the trick of combinations is that it's just like if you can take a deck of cards

right? And you have five cards you draw from a deck. There's lots and lots of different combinations

you can, even if you have only 52 different cards. And so from a modest number of antibody genes on

the order of a few hundred, by mixing and matching them in pieces, we can generate enormous numbers

of antibodies. So the immune system, even with all its powers, can still be sort of beat to the punch

There's still pathogens that can kill us. And this is why we vaccinate. And we understand

And in vaccines, generally what we're giving is a little component, usually a non-living component

not the virus itself, not the pathogen itself, but maybe just a molecule that represents that pathogen

And we're using that to prime the immune system. So we're activating the immune system

So it goes through some of those steps on the staircase, establishes memory

and is poised to respond should we encounter that pathogen. And by being vaccinated, by being immunized, that can save lives, certainly save the suffering

of any particular disease shorten its course save us days off work whatever it might be But this is why we have these vaccine strategies and we seek ways to give our immune system a head start

Because if we don't vaccinate, then we're at risk of suffering the damage that pathogen causes

unless or until our immune system catches up, feeling lousy, or in some cases there's lots of morbidity with these infections

One of the most notorious ones in human history is the smallpox virus, which killed hundreds

of millions of people in human history and even tens of millions of people in the 20th

century until we came up with a vaccine. And there was a global effort to vaccinate virtually every human on the planet

And that eradicated smallpox from the world so that now we don't even vaccinate for smallpox

But that was a virus that moved faster and caused greater pathology than our bodies could keep up with

So we understand this evolutionary process is what drives our adaptive immune system and protects us against enemies from without

But it turns out that sometimes the enemy is coming from within the house

And I'm speaking specifically of cancer. And cancer is truly an evolutionary disease

meaning that it is a disease that results from the exact same evolutionary process we're describing

of the evolutionary process in the external world, of the evolutionary process in the immune system

Cancer forms in the same way. And that is mutations take place in individual cells that if they convey some growth advantage to those cells, those cells may outgrow their neighbors and additional mutations may happen

So they outgrow their neighbors further. And that's what we define as a tumor, a population of cells that is now growing unregulated relative to its normal neighbors

And that's a threat because that unregulated growth can lead to spread throughout the body

can lead to organ involvement, et cetera, and death. But the other concern is, as that cancer gets larger, some of those cells are going to get

yet additional mutations. And some of those cells are going to get yet additional mutations

And so as cancer progresses over time, that tumor is less and less like the cell it started

from and the tumor itself is more genetically diverse. And that's giving us a real challenge

therapeutically. So there is a staircase of cancer. And the way to understand that is that

our risk of cancer is really age dependent. The incidence of cancer goes up really significantly

as we get older. And think for a moment why that might be. And what that is, is it takes time to

climb that whole staircase. So later in life, individual cells have gone through more divisions

They've had more chances to accumulate mutations, mutations that give them some growth advantage

over other cells. And so our risk of cancer grows really significantly as we get into our 40s, 50s

60s, and 70s. So that tells us, not only is it an evolutionary disease, it's a genetic disease

It's mutations taking place in genes that somehow disrupt the normal process of controlling

cell growth. So a huge interest has been, what are those genes? How do we find them? How does

this all work? We first got a hint that cancer was a genetic phenomenon when scientists first

started seeing chromosomal changes in cancers, chromosomes that were broken and fused and things

like this, and that all the tumor cells would have those broken chromosomes or tumors that

rose independently in different people would have those rearranged chromosomes. And that gave us a

okay, something genetically is going on. But the crucial thing was to identify, well, what genes

Well, thanks to genomics, thanks to gene cloning, we now know that there are about 20,000 genes

that essentially run the human body. And we've identified about 150 of those

that when mutated can contribute in some way to cancer. We'll call those drivers

And those drivers split into two classes. One class we'll call accelerators because when they're mutated, they really accelerate

cell multiplication. They also have the name oncogenes, promoting cancer. Another class of genes, they serve as brakes

They hold back proliferation. But if they're disrupted by mutation, then we no longer have their braking function

and the cells can grow out of control. So just like an out of control car, out of control cell proliferation can be due to a

accelerator or broken brake. It can be due to oncogenes that promote cancer or tumor suppressors

would normally suppress that cancer, but they've been disrupted by mutation. So scientists have

banded together across the world to build this sort of catalog of driver genes. And so they

study the state of these genes and all sorts of cancers. And there's some really, really clear

insights from doing this. And the first is, well, it's a multi-hit process. Usually any cancer has

disruptions to multiple genes, might be three, four, five, even seven of these driver genes

And if we look at cancers that arise in kids and compare that with cancers that arise in adults

there's a really profound distinction. When we look in kids, we see there are very few mutations

overall in the DNA of the cancer cell, but they'll be in driver genes. And you don't see many other

mutations that have taken place that are different, say, from mom and dad's DNA. And that's because

a young child, its cells have not gone through that many divisions. It's not accumulated very

many other mutations. It just so happens the mutations that occurred were in these critical

driver genes. It's horrible, heartbreaking, bad luck. But the longer we live, all of our cells

whenever DNA is copied, mutations occur. Now, most of those mutations have no effect. They're

sprinkled among the billions of bases that we have. But every now and then, one of these driver

genes gets hit. Well, the longer we live and the more divisions our cells have gone through

the greater the chance that there have accumulated mutations and eventually hit one or more driver

genes. And once they hit a driver gene, if that cell starts to outproliferate its neighbors

well then those cells in turn may be going through more rounds of division, more mutations

And so now essentially the snowball is rolling such that by later in life, we have cells that

have accumulated a number of driver mutations. And many of our cells at least have one driver

mutation. It may not be pathogenic whatsoever, but a lot of our cells will have mutations in them

some of which could eventually be a problem. So understanding that cancer is this sort of disease

this interplay of mutation and selection, there's really three factors that can contribute to the

formation of cancer. First is just bad luck, that the small number of mutations that are going to

happen anyway, just happened to hit driver genes. Really, that's the explanation

The act for cancer and the kindest thing you can do to any parent whose child is struck

is to reassure them that there was nothing they did to cause it and nothing they could

have done to prevent it. Then there are lifestyle issues like tobacco use and sun exposure

They'll increase the risk of particular cancers, lungs, because that's where the smoke goes

And of course, the skin, because that's what's being exposed to the sunlight

And the third is just age. It's time. The longer we live, the more divisions our cells have gone through, the more mutations have happened

and the more all the environmental things that we've been exposed to have had a chance to work on us

So that later in life, our cells are carrying lots of mutations, and we just hope that none of those cells have sort of that unlucky combination of mutations

that will make it an uncontrollable tumor. So I think there's a few pillars of how we're combating cancer now

that's really different from how we did it before. Now, for prevention, we're looking for these mutations. So you've seen, for example, a product

like Coligard where a stool sample can be sent to a company. Well, they're looking for mutations

characteristic of gastrointestinal cancers in that fecal sample. Okay, so that's early detection

And we know that the earlier you can detect cancer, the better shot you have of counteracting it

The second pillar is to know those cancers and to realize that different driver genes are mutated in different cancers

So instead of treating breast cancer as a monolith, we now subtype breast cancer according to the mutations that exist in an individual's tumor

So it's really important that the genotype, meaning the genetic makeup of a tumor, is yzed when that is first diagnosed

that will shape the treatment course. Because the other thing that oncologists are doing

is they use different drugs, different regimens to go after these cancers

is to study which things work against which genotypes of cancer. So we're now, I think

classifying and categorizing cancers with much greater degree of sophistication. And then there is the specific therapy side

All sorts of drugs have been designed to go after those mutated genes

So to specifically target what has gone wrong in an individual cancer

because of the mutation of a particular gene. Some of these drugs have been spectacular success

Some are doing a good job at, let's just say, buying time

in the hope that the cancer can be contained and managed over the longer period of time

and treated more as like a chronic disease, not necessarily eliminated, but at least managed. Only in the last about 25 years has this really

been possible, but the practice of this has really grown enormously in the last about 15 years

And there's all sorts of new drugs under clinical trials at any given moment. Again, trying to give

a much more specific therapy to the particular alterations that have happened in a given

individuals' tumors. Better prevention, better diagnosis, better therapy. This is driving cancer

rates down, certainly for certain types of cancers, and hopefully going to drive survival

rates up over the long term. These parallels in how life evolves, how the immune system works

how cancer arises, at one level they're startling because the connections aren't so obvious

but fundamentally they're operating on the same process, this mutation and selection

But of course, mutation is a random process. And it's really hard to get our heads around

how can all the diversity and sort of seeming order that's out there in the world

emerge from a process dependent upon chance. Yet, there you have it. Whenever you have

variation and you have competition, natural selection operates and gives us the variety of

life. In the immune system, chance is being exploited. You think, well, we can't leave the

defense of our bodies against chance, but here we're exploiting chance. Now, of course, cancer

has its root in chance, the unlucky mutation that hits a gene that could throw a cell out of balance

with the body. That evolutionary process we've been discussing is one of error and trial

Whereas humans sort of think like engineers, that we think of what we want as an outcome and

how we can get there sort of in the shortest distance. And we may use some trial and error

but we really try to minimize the error. Whereas really these evolutionary processes start with

error. They start with a random change and then try those things out. And I think it's just been

hard for us to get our heads around that. Yet, the more we understand this and all of its

manifestations and the immune system and cancer are two later realizations, we see that this process is a fundamental biological process, random genetic variation

and the sorting of that variation through natural selection. Chapter 4, The Untold Story of Alfred Russell Wallace

So, about 15 years ago on a visit to the University of Cambridge

I happened to visit the archives there, where they hold a lot of original materials from Darwin

And to my astonishment, they brought out and placed into these sweaty hands

a copy of one of the early manuscripts that many, many, many years later would be modified

into the origin of species After Darwin got back from his voyage he was pondering these ideas and he decided to write them down in essay form And by 1844 he completed a 230 essay that fleshed out a lot of his basic ideas

He wouldn't publish anything on evolution for 15 years. That essay, I think, was lost for decades

and found under the steps of his house. So when it was presented to me, all over the manuscript

including on the back pages, there were drawings by Darwin's kids. They had been using it like

scrap paper. It was a spine-tingling moment for me because this was really the birth of one of

the biggest ideas humans have ever had, and I'm grateful that they found it under the stairway

at Darwin's house. So while Darwin's is the most famous figure associated with the theory of

evolution, Alfred Russell Wallace played a key part and deserves huge credit both for his ideas

and for his enormous effort. So really important to understand that the prevailing idea at the time

to which Darwin subscribed and most British scientists subscribed was what we'll call special

creation or the theory of special creation. And that was the idea that every species was

specially created by God and sort of placed or at least emerged in the habitat or in the place

on the globe that best suited it. Now, what started to shake that theory in Darwin's mind

and in Wallace's mind was in the course of their journeys, particularly when they visited

archipelagos, strings of islands. Each of them observed species on different islands that were

slightly different from one another. Now, Darwin, this is just a twist of his story. After nearly

five years at sea and having made a full voyage around the world, they were about to turn

from the southern tip of Africa back up to Europe. But his captain, who was sort of obsessive

decided he wanted to do some more measurements in South America, so he went back across the Atlantic

And Darwin was, at first, just crestfallen that he wasn't headed home

But he needed to make good use of that time, and he started to take his notebooks out

and review what he had seen, but also sort of annotate them

And he thought back to the Galapagos Islands, and he thought back to these mockingbirds that he had seen on different islands

And he saw that on different islands, the mockingbirds were slightly different from one another

in their feather patterns and things like that. And he thought these islands were within sight of one another

just 50 or 60 miles away from one another. If a creator was placing species sort of perfectly adapted to each place

why would these mockingbirds be just slightly different from one another? Now, Wallace's story is more dramatic because Wallace, after four years in the Amazon

really at the breaking point, decided to return to England with specimens and whatever ideas he had collected

And on his way home, his ship caught fire. He had to get into a lifeboat

The ship sank right in front of him with all of his specimens. and he was in an open lifeboat for 10 days hoping to be picked up

And he was picked up, eventually made his way back to England. You'd think after that experience he would have sworn off all voyaging

But two years later he goes back out and does an eight-year voyage across the Malay Archipelago

and collects tens of thousands of more specimens. He noticed, for example, the bird-winged butterflies

These beautiful, incredibly brilliantly colored large butterflies were slightly different from island to island

They both thought in the theory of special creation, these islands all looked alike

Why would there be just slightly different species island to island? And it struck both of them because species could change

Species weren't stable. They weren't immutable, as the theory of special creation argued

They, in fact, changed. And this opened up the big question then

or at least the daring question of, are species the product of natural processes or divinely created

And they thought this was strong evidence that species change naturally. They change according to the conditions they encounter in different places

And the islands were crucial sort of laboratories for understanding this because the volcanic islands of the Galapagos look very similar to one another

but the creatures were a bit different. The islands of the Mali archipelago, very similar foliage and all that, but the creatures

were a little bit different. And the only way they could sort of reconcile that was to say, well, the species were changing

They weren't fixed. They weren't immutable. And as they worked further, they thought about some other patterns

They knew about fossils. In fact, Darwin discovered some really interesting fossils on the coast of Argentina

And through correspondence back home, while he was at sea, he realized these were sort

of larger versions of animals that lived in South America at the time. So he found, for example

giant ground sloths, you know, huge, like eight feet tall ground sloths, much larger than the

living ones. But he realized, hmm, those are extinct creatures. What's the relationship between

the extinct and the living? He's starting to think about that genealogy between the extinct

and the living. And Wallace is also becoming aware of these fossils because he's reading now what's

coming out from the first studies of fossils in Britain in the first part of the 19th century

They had also each read this work by an economist, Thomas Malthus

And Malthus emphasized that there were limits on populations. He thought about the growth of populations

And Malthus said that, you know, disease and famine, that limited, for example, the growth of populations

Well, Darwin and Wallace, being out of nature, they understood that life was very tough

They understood that really life was a battlefield, a contest, and that far more young are produced

than can survive to adulthood And what uncanny is when you look at the writings of each of these individuals Darwin notebooks Wallace draft manuscript they use the same language

They describe life as, quote, a struggle for existence. Exactly the same words, unbeknownst to each other

And they talk about variations, however slight, and that they could be favored

And that led Darwin to coin the word natural selection. they'll be selected for in nature. And the things that are disadvantaged will be selected against

And Wallace said essentially the same thing, that one could imagine if there's a slight advantage

that slight advantage will be passed on generation after generation. So Darwin for 20 years is back

home in England. He's well known because right after he did the voyage on the Beagle, he wrote

the book that we call today The Voyage of the Beagle. And it was a popular read. It's a great

read. It's still a great read today about his travels. And he was an eminent naturalist

Wallace was an unknown. He was from far more modest upbringing, and he was really paying his

way on his voyages by selling a fraction of the specimens that he was collecting. So he was

thousands and thousands of miles away from the center of science in England, and he wasn't

connected really at all. So Wallace, by 1858, has a pretty good idea that life changes, life evolves

And he writes up a very short account of his thinking about how that works. And he decides

to send it to the one naturalist with whom he struck up a correspondence who thinks might

appreciate it. He sends it to Charles Darwin. Well, this event rocks Darwin because Darwin has

not gone public with his theory of evolution. And now here's this faraway correspondent, 7,000 miles

away from England, who in just a few pages has essentially the same idea that Darwin has, that

Darwin's labored on for about 20 years. Well, Darwin's friends rally and decide that the best

thing to do would be to read Wallace's paper and an excerpt from Darwin's work in front of a British

Scientific Society to sort of put both of these ideas out in the public. Darwin wasn't there. It

turns out Darwin had suffered tragedy. He was burying his Charles Jr., one of his sons, on the

day this paper was read. And Wallace was 7,000 miles away, didn't even know what was going on

It really didn't make much of a splash. Not much attention was paid. But the next year is when

Darwin published on The Origin of Species, and that's when everyone paid attention

The response and acceptance or rejection, particularly to Darwin's Origin of Species

because that's the book everybody could put their hands on. It sold out in its first printing

It was reprinted quickly. It was translated into other languages. American versions were made

So people who are interested in science, biology, natural history around the world

could get their hands on Darwin's ideas. So their reactions were a very wide spectrum

Thomas Huxley, who was one of Darwin's close confidants, sort of thought, you know, wow

why didn't I think of that? He thought it was, you know, compelling and sort of obvious

But I think one thing to appreciate with Darwin is that his book is extraordinary in that

he also presents and yzes the critiques of his own theory. I mean, imagine that

This is just something that human beings don't generally do. If they've got an idea, they're going to put out all the evidence in favor of their idea

And they're usually not going to present to the opposition all the evidence, either against it or all the evidence that's missing

But Darwin did this in a masterful way and basically often saying things like, you know, if something, if a particular thing was found, it could crush my theory

Or if my theory is true, this would be true. But there wouldn't necessarily be any evidence weighing on that

So it was a masterful presentation. And I think that made it very accessible to people

They understood the strengths and weaknesses of the theory. And then new discoveries could be interpreted in light of that theory

And as some new discoveries, particularly from the fossil record, came to light

well, that gave a lot of power to Darwin. Because Darwin at the time Origin of Species was published

the fossil record was pretty skimpy. But Darwin made some really strong predictions about what should be found

for example, in the fossil record. And one of those was transitional forms

if the tree of life has evolved in the way that he said

there should be forms that are intermediate between existing forms today. And two years after the origin of species, a fossil called Archaeopteryx

which has got mixed characteristics of both birds and reptiles, was discovered

And I mean, you couldn't have drawn anything better than that fossil for supporting Darwin's theory

So I think the reception of the scientific community, some of it at first was positive, but there were long, long holdouts

There were career-long holdouts against Darwin among even very eminent natural historians, biologists, and scientists

And that holdout was really for reasons we'd all recognize today. While Darwin didn't, in 1859, didn't comment directly on the evolution of humans

he did later in 1871. Everyone knew that humans were going to be a touchy subject

because for at least a couple millennia, the thinking was that man was created in God's image

not descended from some previous animal forms. But clearly Darwin's theory would be interpreted to say that

No, humans, just like every other animal, evolved their anatomy and their physiology

from pre-existing forms. And some scientists held out on that point both perhaps from their own viewpoint of faith but also I think because of some pressures in the academy Darwin was on the short list to be knighted When the origin of species came out

well, he never got that knighthood. So, you know, this was an idea that many people found repulsive

They were really worried about the societal implications to sort of take the creator out

of the immediate picture of sort of, you know, tending to human affairs. And that's, of course

still a struggle that exists to today. And, you know, scientists, you know, being part of society

it was not universally, you know, accepted, far from it. Where Wallace really finally grasped the

scope of what Darwin had been working and thinking was in 1859, when The Origin of Species was

published. And he received a copy of The Origin of Species. And he read it and re-read it. In fact

Wallace's own copy is in the Natural History Museum in London, so we can understand sort of

his reactions in real time. But I think one of the most poignant things I know in the history of

science was Wallace's put his thoughts and reactions in a letter to his close friend and

confidant, Henry Walter Bates, with whom he had first traveled to the Amazon. on. And Wallace is just gushing with admiration for Darwin. And he says, I never, given any amount

of time, I could have never come up with something as massive and compelling as Darwin. And he said

I don't think any branch of science has ever been created by an individual such as this, such as

Darwin. So Wallace was in awe of Darwin's synthesis, which was the origin of species

But they were mutually generous to each other. Darwin, right off on page one, acknowledges Wallace and Wallace's ideas

And Wallace later, for example, when he writes his first major book, he dedicates it to Darwin

They are mutual admirers to the point where, for example, Wallace is going to be a pallbearer at Darwin's funeral

And in their day, this was referred to as the Darwin-Wallace theory

it's only later that biologists and historians just started kind of forgetting about Wallace

and crediting Darwin now there might be reasons for that Darwin came from a wealthy family

the University of Cambridge did a great job at sort of amassing Darwin's collections and

Darwin's writings and so we just have a better historical record of everything that Darwin did

But at the time, it was the Darwin-Wallace theory. And I think by today's scientific standards, given the genesis of this theory, the theory

certainly of natural selection by the two individuals, we would be crediting both of them

And it's just, you know, it's just the unfortunate sort of, you know, accidents of time that

people kept talking about Darwin and Wallace sort of faded to the background

But I really feel in the last 25 years or so that Wallace has seen sort of a renaissance and that people are much more aware of Wallace's huge contributions

And then Wallace outlived Darwin by 30 years. So he was a really important figure in the discussion of evolution because, you know, this was a brand new science

It had relatively few advocates at the beginning, certainly people that really understood it well

And so Wallace played a huge role in getting people to help understand these ideas

I think if Darwin and Wallace were alive today, they would be so overjoyed

by the detail with which we understand the process that they first figured out

They knew variation was important. They knew variation was the fuel of the evolutionary process

Had no idea how that variation arose. Now, any biologist can point right to the DNA in a newly hatched creature and say

there's the mutation. That's what's going to make the difference. So our understanding of the material basis of evolution is phenomenally strong

And I think that would be extremely gratifying to them. But these other manifestations, the role it plays in health and disease

were nowhere in Darwin and Wallace's minds. So I think that would, again, further astound them that this process they figured out had such widespread ramifications beyond just the natural world

What we've seen are striking parallels in how life evolves, how our immune system works, and even how cancer arises

This process of mutation and selection, this staircase. So really, the process that Darwin and Wallace had that first insight into is a universal process

Wherever there's variation, wherever there's competition, selection will operate. For me personally, as an evolutionary biologist, this just underscores the explanatory power of evolutionary theory

and the importance of understanding the evolutionary process. You might think, well, the evolutionary process, let's just leave it to the scientists to worry about it

But I think in our daily lives, you understand that this is why we vaccinate

This is why we are now developing these strategies against cancer that we, of course, hope everybody will be able to benefit from

That's a long way from the Beagle voyage of 160 years ago

But that's fundamentally where Darwin and Wallace have brought us. want to support the channel join the big think members community where you get access to videos

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