According to statistics published by FAO,
it is estimated that on our planet about one billion people
are, to some extent, undernourished, they suffer from hunger.
This is especially relevant when it comes to children,
and the deficiency of animal proteins
that influences their physical and intellectual development,
and may cause, in the long term, important deficits.
Animal proteins come from farm animals.
Animal breeding has historically evolved with the evolution of civilization;
and today, according to FAO statistics,
we roughly breed 3.5 billion animals,
excluding birds and fishes,
which means one farmed animal every two people on Earth.
These animals also have an impact on the environment
and by breeding them we generate a number of major environmental issues.
A large number of these animals
is located in climatically challenged areas,
so the productivity of these animals is rather low,
while in countries with advanced zootechnics
we have less animals, but much more productive.
To give you an idea,
if in 1950, in the Po Valley,
a Friesian dairy cow gave 4,000 kilos of milk,
today with the same products, the same soil and and the same technology,
but with different genetics,
we can extract from these cows more than twice the amount of milk,
Therefore, the selection and genetic improvement of animals
for animal protein production
played a pivotal role
in countries with advanced zoo-techniques,
while it plays no role yet in areas of the planet
where animals are still raised in a, say, primitive state.
What is the tool that allows us to improve the animals we breed?
This improvement is brought about through reproduction technologies,
From the 1950s onwards, in particular,
artificial insemination has been the main tool for genetic improvement,
In other words, the semen of superior animals
has been distributed through on-farm insemination
and this has resulted
in the productive increase that I have just shown you.
Other technologies were developed over the years,
always with a view to speeding up
this process of selection and genetic improvement.
In particular, embryo-related technologies
have led to an increased exploitation of the female germline:
with spermatozoa we use the male;
with ova, instead, we exploit the genetic value of females.
In particular, the production of in vitro embryos
is a recently acquired technology
that allows us to produce large numbers of test-tube embryos
and now we’ll see how.
This technology has also created the technological premises, the know-how,
to develop cloning,
which is the topic we are dealing with today.
In turn, cloning laid the foundations
that allowed us to make genetic modification,
or animal transgenesis - similar to the one used for plants -
a further tool in our pursuit
of genetic improvement of farm animals, and not only.
A few words on in vitro technology now, as it paved the way for animal cloning.
Today, in a laboratory, we are able
to take gametes, the ova from females and the sperm from males,
and obtain fertilization in a test tube -
in vitro technology is synonymous with test tube technology -
obtain the first stages of embryonic development,
obtain an embryo that can be at this point either implanted in a receiver, or frozen.
So the value of this technology
goes beyond the applications that have been used so far
and the value of this technology
has resulted in the awarding of the Nobel Prize for Medicine
to the pioneer on humans of this technology,
which has led to the birth
of over four million people around the world.
So, in vitro technology is crucial to achieve cloning.
Now, let's examine in greater detail what we are going to talk about.
The term cloning is improper, often used inappropriately
and it creates ungrounded fears.
Technically speaking,
we talk about somatic cloning or cell nuclear transfer,
because cloning consists
in transferring into an egg cell the nucleus of a cell.
But, before we go into further detail, what is meant by cloning?
It means creating two animal organisms,
that is, two living beings with the same genetic makeup.
All of you, I think, know sets of homozygous twins,
that is, two absolutely identical individuals.
Technically, we can define them clones, so homozygous twins are clones.
With cloning in the lab we create homozygous twins,
although they are born at different times.
But to understand cloning even better,
consider that it has always been practiced in agriculture,
because from a simple cutting of a plant
we generate a new plant, which is therefore cloned.
Most artificial forests or tree plantations, or fruit trees,
are obtained by cloning;
and we eat this fruit,
we use these materials that are of clonal origin,
but no one has ever raised any objection, as far as plants are concerned.
The issues, when it comes to animals, are different and more complicated,
which is understandable.
The first historical example of cloning
appears in the Bible, with the story of Adam and Eve.
As you may remember, Eve was obtained from a rib taken from Adam while he slept,
so that is possibly the first example of mammal cloning,
but it didn't work very well, clearly, as they were not exactly the same,
indeed they were of different sexes.
Later on, the first examples, or at least attempts, of cloning
were made with simple animals.
Here on your left you can see an example, dating back to 1928,
when researchers tried to recreate in a lab
what happens spontaneously in nature when monozygotic twins are formed,
that is, monozygotic twins originate from the bisection of the embryo,
but the number of clones we can produce this way is rather limited.
Instead, in these experiments on frogs, in the '50s,
they worked with nuclei taken from adult animal,
which meant every cell is enucleated,
with all the genetic information it takes to create an individual.
These researchers introduced these nuclei into frog eggs.
However, they never succeeded in obtaining adult animals,
but only tadpoles,
which are the stage before metamorphosis.
The same experiments were carried out unsuccessfully on mice,
so, in 1983 some researchers claimed
that it was impossible to clone animals
starting from adult cells.
In 1986, the first clones of domestic animals
were obtained using cells taken from the embryo
just a few hours after fertilization,
when the few cells that make up the embryo
are still undifferentiated.
Briefly, how do we go about it?
As you will have understood, we need the genome,
which is to be found in nuclei of cells.
So we start with a biopsy taken from an adult animal,
which can also be an animal that has just been slaughtered
or even a dead animal.
These cells can be multiplied in vitro, so in a laboratory,
or they can also be frozen in liquid nitrogen,
and preserved for decades.
Then, since we are not dealing with plants, we need an oocyte,
because we have to put the genome in its natural environment,
so that it may develop,
and we use, just like everyone, oocytes taken at the slaughterhouse.
As the 20th-century naturalist who coined the motto “Ex ovo omnia” used to say,
everything originates from the egg, which is quite evident.
Since we work with farm animals which eventually end up being slaughtered,
we find plenty of oocytes for our experiments
in the slaughterhouse.
However, we must remove from the oocyte its genetic information
and we must replace it
with the genetic information of the animal that we want to clone.
So we introduce the nucleus,
we have the activation of the embryo thus formed,
and this embryo is implanted in the uterus of a surrogate mother,
giving life to a genomic copy of the original animal.
So I have proved that it is possible to get twins
that are different ages because they are born at different times,
but from the genomic point of view they have the same DNA.
This is the first bull we obtained in Cremona in 1999, Galileo.
These are embryos,
just so you see what they’re like when they're put in utero,
they are still undifferentiated,
you can’t distinguish the parts that will form the animal yet,
and anyway there are no major differences between one species and the other.
This is Prometea, the first colt obtained with this technique,
She is the first filly, the first equine clone in the world,
and if I did not tell you that it is a clone,
you would consider it a normal animal,
without any particular problems,
and even if the efficiency of the technique,
in terms of animals born,
is lower than natural reproduction,
these animals are born absolutely normal
and the proof that they're normal is,
they are able to have a normal offspring, when they grow up.
Here, on the left, you can see Prometea
and her son Pegaso behind,
obtained by artificial insemination.
The same can be done with cattle.
We have cloned several specimens of superior bulls.
This picture represents the clones
of a very important reproducer for the Friesian race,
which died several years ago,
and shows the genetic potential of this animal
that could be distributed, I think, in a future perspective
to those areas of the world that do not have our advanced genetics,
allowing them to quickly benefit from reproducers like this,
that would normally come at unaffordable prices.
A number of mammals have been cloned with this technology.
The technique is reproducible and certainly perfectible.
Here is Dolly, the first adult somatic cell clone obtained in 1996,
and then a number of other mammals ending with the camel cloned last year.
Besides allowing us to reproduce genetic copies of animals,
cloning has opened up another perspective: genetic engineering.
This instance of genetic engineering has nothing to do with cloning
but gives you an idea
of how much powerful - and even scary - this technique could be.
These are two mice, two brothers.
The rat growth hormone was inserted in the embryo of one of the two,
so it grew the size of a rat.
Of course doing this kind of manipulation on farm animals is much more complicated,
which is why the idea of working in this direction
was only acted upon once cloning became available.
I already shared the technique, so where's the difference?
Nowadays, using fairly reproducible and safe techniques,
I can engineer somatic cells
taken from an animal and being cultivated in a laboratory.
I do my genetic engineering operation:
I can insert genetic characteristics that interests me,
or I can remove negative characteristics;
or I could intervene on genetic defects or mutations.
I then take these cells,
I follow the process I already described to you
and the animal that is born is no longer identical to the original -
or better, it resembles it closely,
but in addition, it will have the feature I introduced and modified.
As I was saying, thanks to these systems, we can now engineer large animals,
which could not be engineered previously.
By way of example, here is a line of pigs in which we produced a marker,
which is a protein taken from a marine jellyfish,
that makes them fluorescent under blue light.
This is an example of a line
that serves for research and experimentation,
as we can trace the cells,
but above all, if instead of using green
I use a genetic disease, or something else,
I can create animal models.
In particular, we are working to engineer the pig genome,
so that pig organs may become compatible with human organs.
This means that pigs in the future will no longer be bred only for ham,
but may also be used as a source of organs for transplantation in humans.
There are also applications in the field of animal husbandry.
For instance, Canadian researchers
have engineered pigs that can assimilate phosphorus.
As you know, when it comes to pig breeding,
pollution is a major problem,
because pigs release large amounts of phosphorus in their droppings,
which ends up in the sea, eutrophicates the environment
and results in the proliferation of algae.
This pig has been engineered so as to produce an enzyme in its saliva,
enabling it to digest organic phosphorus, thus making it less polluting.
Or this other example of a pig rich in Omega 3 acids.
Everyone knows
how beneficial these acids are, how good for our health,
and it is possible to get a line of this type.
Or let’s take cattle: for example,
the cow you see in the picture is cloned
and was obtained by inserting an antibacterial,
so this cow has in its milk a natural antibacterial,
which makes it resistant to mastitis.
Mastitis is the main cause of infections on dairy farms,
and tons of antibiotics are needed to treat the animals suffering from it,
with repercussions on animals’ health.
Thanks to this operation it is possible to solve the problem,
or at least significantly reduce the use of antibiotics,
which is also beneficial for us
since it causes resistance to antibiotics in humans,
which means doctors no longer have means to treat us when we actually get sick.
Another example is that of being able
to produce drugs in genetically modified animals,
this is already a commercial product:
a goat, obtained by means of cloning and genetic engineering,
which produces a substance that controls the buildup of blood clots.
This means, that patients who need this molecule
can now get it in larger quantities and at lower prices,
since by producing it in animals, in goats,
it is possible to produce larger quantities,
and especially for certain drugs containing complex molecules
that bacteria are unable to synthesize.
To sum up, I would say that regardless of the implications of the research,
cloning has opened up new perspectives,
new ways of perceiving and approaching basic biology,
which, unfortunately, I don't have time to go into now.
Anyway, even limiting ourselves
to the potential impact for us ordinary people,
I can tell you that there are two applications,
in the zoo-technical and biomedical fields.
So cloning is important not only for agriculture,
but also for our health.
Obviously it raises a number of ethical issues,
mainly in developed countries.
Maybe other countries are less concerned
because they need new technologies and new opportunities.
But there is an ideological stance when it comes to these new technologies,
therefore often a groundless stance,
and I think that being able to explain, with the utmost transparency,
to the general audience,
the opportunities brought by science,
is definitely a thing to do
and can help change, I think, among the general audience
the perception of this technique.
Thank you.
(Applause)