The benefits of animal cloning Ι Cesare Galli Ι TEDxLakeComo

He is a founding partner and Managing Director of Avantea, of which he is also a researching manager into animal cloning sector and transgenesis, in order to create animal models for biomedical purpose.

This talk was given at a TEDx event using the TED conference format but independently organized by a local community.

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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)