Translator: Amaranta Heredia Jaén Reviewer: Sebastian Betti
Alberto Kornblihtt: genes, evolution and us
I like to think biology as the science that
deals with similarities and differences in the living world.
For example, here we have a fern, a pine and a rose.
The three of them are vascular plants.
But, how do they differ?
Well, the fern is a seedless plant.
The others have seeds, but the pine has naked seeds
and the rose has them in an ovary.
Here we see three mollusks:
The octopus, the squid and the clam.
How do they differ, apart from the clam not being
in its own environment, but rather in ours?
The octopus and the squid don't have a shell.
The clam does.
The octopus doesn't have a pen.
If you ever cooked paella and had to clean squids,
you know what a pen is.
Basically, it is that cartilaginous, transparent part
that squids have inside.
Here we see the shark, the dolphin and the killer whale.
The three of them are hydrodynamic and live in the water.
However, the shark - the three are vertebrates -
the shark is a fish.
Its ancestors were fish.
Whereas the dolphin and the killer whale are mammals
with two specific mammal characteristics:
They have hair and they produce milk.
If we focus on their differences,
their ancestors were quadrupeds that lived on the earth
and looked like cows.
Therefore, their hydrodynamic adaptation is secondary.
What's the difference between the dolphin and the whale?
The dolphin is friendly and the killer whale not so much.
Here we see other differences.
They belong to the same species, Homo sapiens sapiens.
Magic Johnson has black skin
and Manu Ginóbili (whose image today is from a recording)
has white skin.
Now, differences can be applied to the virtual world as well.
Film maker James Cameron produced these two creatures
who live in the imaginary planet Pandora.
Neytiri is different from Jake Sully because she's a Navi
and Jake Sully is an Avatar.
That being so, Jake Sully has human DNA
and, therefore, he has five fingers
and [Neytiri] has four.
I'm sure that many of you who watched the film
will try to watch it again to check if I'm right.
Yes, I am.
All this is located in a molecule
that contains our genetic information, the DNA.
The deoxyribonucleic acid.
I can't explain now how that genetic information
is coded in our DNA,
but I can tell you that there is a but.
A but meaning that all the characteristics that I've just told you
are coded in the DNA information.
But there are differences among the living organisms that have nothing to do with the DNA,
but with the environment.
For example, the Argentinean Vice-President Julio Cobos
and the former Argentinean President Fernando de la Rúa
both belong to the species Homo sapiens sapiens.
And some seriously discuss whether they should
belong to the subspecies
Well, these two people are obviously very similar
--everyone agrees--
but their similarities are not genetic, but environmental.
They relate to their ideology, their deficiencies, their abilities,
to things that happened to them
during their lives and also probably
because of the stimuli they received during their intrauterine lives.
Why?
The phenotype is the irreversible union
of genotype and environment.
In some circumstances, genes are predominant.
In others, the environment does.
What is the phenotype?
The phenotype is the aspect, the morphology,
the physiology, the behavior.
The genotype
The environment, just that.
The DNA structure is a double helix
formed by something like chemical letters
called bases, which give an order
to the cells to produce proteins.
The DNA structure was discovered in 1953
by these two well-known scientists:
James Watson and Francis Crick.
Francis Crick died in 2004.
They both received the Nobel Prize in 1962.
James Watson still lives.
During the last sixty years, he's witnessed
a revolution, not only a scientific one,
but also a revolution of industry,
society and everyday life.
Because upon discovering that genetic information
is contained within the DNA,
many aspects of our lives have been revolutionized.
Here we see Crick with a slide rule.
This photographer asked Crick in 1953
to point at the DNA structure with a slide rule.
I checked yesterday that none here under 40
knows what a slide rule is.
Here you can see.
It's a tool to calculate square roots,
logarithms, multiplications and divisions
without any electronic device.
In 1953, it was not the time of an initiative like
One Laptop Per Child,
but rather of a slide rule per child.
Slide rules were not massively distributed,
but I just wanted to point out the historical context.
The revolution that Watson witnessed
- and keeps witnessing -
involves medicine,
things like the diagnose of hereditary or infectious illnesses and cancer,
or medicines produced by recombinant DNA technology:
interferons, erythropoietin, growth hormone, insulin.
Recombinant vaccines, like the hepatitis B vaccine,
which most of you, or many of you, have taken.
It has been produced through genetic engineering.
Gene therapy, although not used on a daily basis,
has gone a long way in research.
Genetically modified animals.
Personalized medicine in the future.
Monoclonal antibodies, created by our Nobel Prize
César Milstein.
In forensic pathology,
the determination of identity and family ties.
I will focus for a moment on this topic,
as it is quite relevant to our country.
The study of differences and similarities in DNA sequences
has let our country lead the determination of identities.
Specially, the identification of the children of missing people
and their biological ties with their grandparents.
Some people have said that mitochondrial DNA analysis
seems to have been designed especially for the grandmothers of Plaza de Mayo.
I would like to reflect upon something here.
It is essential to use DNA analysis
to find out the truth in the case of
the children of Ernestina Herrera de Noble.
As biology makes differences among species,
biology can also distinguish between
an adopted child and a biological child.
That's a truth Argentina
cannot hide any more.
(Applauses)
Industry and agriculture also uderwent their revolutions.
We had and we have the pharmaceutical industry of recombinant DNA,
the production of enzymes for industry,
food poisoning detection,
genetically modified animals
-area in which Argentina pioneers-,
stud's semen classification,
stolen livestock identification,
genetically modified plants produced in our country,
the expansion of soybean production and also our fiscal surplus.
I will go deeper in these examples.
I guess you don't know it, but I brought
a pair of not worn jeans.
Every pair of worn jeans sold in the world today
has been worn out by an enzyme produced by genetic engineering.
The so called stone washing doesn't exist anymore.
Jeans are not washed with stones in the industry.
They wear them out with cellulase, which is produced by a fungus.
Jeans are made of cellulose,
cellulase deteriorates them. That fungus has a gene
which has been transferred to a bacterium.
Bacteria are grown industrially and they produce the enzyme
which is used by denim factories to sell their jeans.
Look at how much the technological and biotechnological
revolutions affect our daily lives.
Everybody buys worn jeans.
Well, chromosomes are found in cells.
DNA is found In chromosome.
DNA is divided in different segments called genes.
Every gene is copied in order to make another nucleic acid called RNA.
This RNA is copied to make a protein,
which is the final product and performs its function in our cells.
Proteins are like cell workers.
This starts to get complex and it is related
to the topic I want to share with you.
A gene is basically made up of
alternating segments
called exons and introns.
When they are copied, both of them are copied: exons and introns.
But before the second copy takes place,
the RNA eliminates the introns
-it throws them away-
and it binds the exons together.
That process is called splicing,
which basically means "cut and join",
and is taking place in your cells right now,
simultaneously, all day long
in all of your genes.
You produce long RNA that is made shorter.
Until the 80's, it was widely believed that every gene
produced only one protein.
Nevertheless, in the mid-80's,
they discovered a gene that produced many proteins.
This process is called alternative splicing,
and it is a variant of the splicing I just mentioned.
This complex variant implies the following:
if the gene has exons and introns,
when it is copied, the first copy duplicates an RNA
with exons and introns, but the splicing
can take place in two different ways.
It may either include or exclude the exon in the middle,
therefore, the gene can produce two different proteins.
And this gets even much more complex,
as our genes are capable of producing hundreds of proteins each.
Now, alternative splicing is likely to be the cause
of vertebrates' great complexity.
That's us.
Why?
Look, this microscopic worm is called Caenorhabditis elegans,
and it is a one-millimeter microscopic invertebrate
formed by a thousand cells.
Each of those cells contains 19,000 genes.
That's ok, numbers don't mean anything.
This other animal, called Madonna,
belongs to the species Homo sapiens sapiens.
We can easily see that it is a macroscopic vertebrate,
it is almost 2 meters high and it contains 10 raised to the 13th power cells.
Which is 10 British billions of cells (10 US trillions),
and it has 23,000 genes.
Even if we'd like to avoid being human-centric,
it is obvious that Madonna and us are far more complex
than that pitiful microscopic worm.
Nevertheless, our number of genes is quite similar.
Where is the difference, then?
Firstly, we have to know what is false:
We are not more complex because of our number of genes.
Secondly, even if 19,000 and 23,000
are similar figures,
this worm can produce 25,000 proteins with 19,000 genes,
while with our 23,000 genes we can produce
around 100,000 proteins,
because 80% of our genes are able to
produce more than one protein through alternative splicing.
This means that our vast complexity has to do
with the great amount of proteins we can produce.
When I say 'we', I mean vertebrates:
mammals, birds.
I don't mean just humans.
So, we have seen that our genes
can produce many more proteins than the worm's.
Now, the alternative splicing
-which we study in our lab-
is very important in the cause of many illnesses.
To give you some examples, I can mention:
breast, renal and gastric cancers; hereditary diseases,
like Fragile X syndrome or myotonic dystrophy,
or cystic fibrosis.
Let me give you an example
which is not an illness and it is nort even proved,
but it shows how alternative splicing
relates to our everyday life.
Look, this is an ear.
Inside, we find a sensory device, the inner ear.
If we look at the ear, inside of it, in the inner ear,
there is something called the cochlea.
Inside the cochlea there is a fluid which vibrates when it receives a sound wave.
Within this fluid there are some cells called hair cells.
Hair cells are just little hairs.
Those hairs have some channels inside, there in green,
they are in the membrane and they can be either closed or opened.
Outside, in the fluid, there are salts, ions.
When sounds hits and make the fluid vibrates,
the hair cells move mechanically.
As they move, they open the channels,
the ions get in and there --where the arrow is pointing--
an electrical impulse is generated that goes to the brain
and makes us feel the sound.
The issue is that along the cochlea,
cells perceive different sound frequencies.
We can perceive different frequencies.
And it is believed that each green channel
in every hair cell
is a different variant of alternative splicing.
What does this mean?
That our capacity of perceiving different frequencies
is related only to one protein of the channel
--I don't know if it has several polypeptides, that’s technical stuff--
The proteins' variants
are adapted to perceive different frequencies
and to produce nerve impulses
of different magnitude depending on the frequency.
In other words, we can say that alternative splicing
is like music to our ears and it allows us to distinguish,
for example, Beethoven
from the Beatles.
How is alternative splicing controlled?
In the two minutes left I will put
in two slides twelve years of research
of our Exact and Natural Sciences Faculty's lab,
of the University of Buenos Aires.
I mentioned that if the enzyme that copies the gene
and makes the RNA is slow, it allows to discard the introns
one by one, to get an RNA with all the exons.
The result is a variant of alternative splicing for each gene.
Nevertheless, if the copying is fast,
the section with the inner exon will be eliminated,
introns cannot be eliminated individually
and that produces a different variant.
We found that the copying's speed
partially determines the result
of which protein variant produces each gene.
Not long ago, we also found that the copying's speed
is highly limited by the gene structure in the DNA.
The DNA is not naked.
It is covered by proteins, which are called chromatin.
That chromatin in the nucleus can be either loose or compact.
If it is loose, the copying is fast.
If it is compact, the copying is slow,
as the little truck shows here.
It's the difference between driving on asphalt or on gravel.
On gravel one should drive slower,
because of the many obstacles.
I still have 55 seconds left. These two slides
show 12 years of work of our research group
done in the Exact Sciences Faculty
in the IFIBYNE Institute of the CONICET,
whose director is here among the public,
at the University of Buenos Aires.
They advised me not to say anything but I can't help it.
The University of Buenos Aires is a public university, a State university.
It is free, autonomous, (applauses)
co-governed, secular, mass-attended,
scientific and technological, and of excellence.
(Applauses)
I brought an epilogue, but I won't show it.
This is all. My idea, if TED is a place for ideas,
or to share ideas, the one on the last slide
is basically a counter-idea.
In the 90's they tried to convinced us that
education had to be privatized,
elitist and exclusive of private universities.
You know it already, if you know me:
I am a defender of public university.
But that’s not whimsical.
Our daily experience shows that public university,
under the conditions I mentioned,
is the natural place to grow knowledge.
Private university can try to aim
to produce knowledge, but it doesn't achieve it.
It doesn't make it, because it lacks
many of those factors.
Thank you very much.
(Applauses)