Transcriber: Zsuzsa Viola Reviewer: David DeRuwe
Surely, most of us have been faced with the increasing price of drugs.
There are many reasons for this cost escalation,
and one of them
is that pharmaceutical companies are spending billions of dollars
just to develop the drugs.
Just in the United States annually,
the global pharmaceutical industry spends about 70 billion dollars.
And of course, they would like to recoup this money.
But there is one point in the drug development process,
which is really critical,
and which is really the cause of this increasing cost.
And it is when the developmental process
goes from the preclinical trials to the human clinical trials.
And about 20 to 50% of the drug candidates fail here,
with severe financial consequences for the developer.
If we could use engineered human tissues -
because the problem is that humans are not animals,
at least not most at the time,
and that's why the animal trials don't necessarily help.
But what if we could put engineered human tissues
to interface those two points in the drug development process?
Surely, if the drug does not work on the engineered human tissue,
well, there's a great probability that it's not going to work in the human,
and if we are in this endeavor successful,
then we can imagine
that we could eliminate entirely animal trials.
And that would be great
because animal trials are becoming more and more controversial anyway.
So a few years ago, we developed the technology
based on the three-dimensional printing of cells
that allows us to create or rather to build
extended living structures such as tissues and organoids.
And this technology works somehow like this:
So we use a bioprinter, which is a three-dimensional printer,
except that it puts down the bio-ink particles,
which are discrete mini tissues,
at least in the incarnation of the technology in our case,
and those could be aggregate, spherical aggregates,
or cylindrical units, discrete units that are composed of living cells.
On my right, you see the animation
depositing the spherical bio-ink particles,
and their reality, the white stuff, is cellular material,
and everything is deposited in according to a template,
which is consistent with the structure we want to build.
Now, there was one very important point in the schematics, the bio-ink particles,
those discrete, little, teeny-tiny tissues fused post printing.
And that's a very important thing.
That's really where the magic happens.
We don't control that process,
but tissue fusion is a fundamental embryonic-developmental process.
Most of our organs come together by the fusion of simpler structures.
And that's what is being used in this process.
And with this technology,
we were able to essentially start a company,
and the company is called Organovo,
and the company builds tissues for drug development, drug testing,
simple organoids like vascular grafts -
here are rank examples of those of nerve grafts -
and this technology really is one of the many technologies
that today are being used in tissue engineering,
or more generally,
by practitioners of biofabrication.
What spectacular progress has been in this field in the last few years.
New replacement organs like bladder or trachea or skin or bone
have been produced in many laboratories in the world
and implanted in many hospitals into humans,
and by this improving the quality of life of many patients.
When we realized that we can be successful in medicine and in pharmacology,
we asked ourselves the question,
"What else could we do with this technology?
So we can build three-dimensional living structures.
But what else could we do with it?"
And as we were contemplating this question,
we realized that when we are chewing on our favorite steak,
or wear our favorite leather jacket,
we very seldom think about the place of their common origin.
And what is that?
It's a hidden, well-guarded, not-so-happy place
neither for the animals nor for the people who work there -
it's the slaughterhouse.
And I've been in slaughterhouses, and I don't recommend anybody going there.
So imagine
if leather and meat could be built,
could be produced without killing animals,
with much less use of resources.
That would be fantastic.
Did you know that just a quarter pounder,
a roughly 100-gram hamburger,
requires this input of resources?
It's just insane.
Say, using 200 liters of water
just to gobble up this little piece of burger?
Not talking about the greenhouse gases that are being released in the process.
Or did you know that today, where today we the 7 billion people on the planet
sharing it with 60 billion land animals will grow,
and those numbers
respectively will reach 9 billion and 100 billion by 2050?
And those 100 billion animals,
they aren't just the source of our meats
or our leather goods or our food in general;
they are the consumers of the same resources that we need.
And they are the biggest polluters of our environment.
So just think about those animals in close vicinity -
it's a breeding ground for disease, for harm and abuse.
This cannot go on like that.
There has to be something has to be done about it
because we're destroying our environment,
it causes serious harm to our food security,
and there's a consequence to public safety.
So it seems there is another way.
There is another way to build leather,
and it is my task today to convince you
that leather can be produced in a much more ethical way.
I'm going to concentrate on leather which we wear, which we carry,
as opposed to meat which we ingest,
and therefore it's much more probably controversial.
But I hope that by convincing the public, that is you,
that we can build cultured leather
in an ethical and otherwise acceptable way,
it will be easier later on to introduce the notion of cultured meat.
So how do we do this?
We go back to the basic building blocks of life: the cells.
We source the cells from the animal through harmless biopsy,
we let those cells,
under laboratory conditions, to grow to the sufficient numbers,
and while those specialized cells are growing,
they secrete among others a protein,
the protein collagen, the most abundant in our body,
which is the major component of skin,
and at the end of the day,
is the major and critical, most significant component of leather.
And so once we have enough collagen,
we harvest the collagen, we form the collagen into sheets,
we take the sheets and couple the sheets together
creating thicker sheets, and eventually,
we take this multi-layered hide
and we tan it.
And the tanning takes place in specialized facilities,
and at the end of the day, we have our cultured leather.
Now, this what you see here is a beer brewery.
Wouldn't it be beautiful
if we could do the entire process that I just described in such a facility,
which is transparent, clean, appealing?
After all, the process that I showed you in the preceding slide
is something that we can control from A to Z.
Every step in that process could be performed
under the roof of a single facility - something like this.
The big containers here are used to ferment beer,
but we could imagine them, used to ferment the brew - cells.
At the end of the day,
beer brewing or yogurt making
are old well-known biofabrication processes,
and we can borrow from what we know from those processes.
So this is where we would like to go.
We would like to do it in this totally transparent way.
People could tour such a facility, could walk in, see the entire process -
you could never do it in an abattoir.
So let me show you some pieces of this cultured leather.
We are still at the beginning of the journey,
but we have produced already various samples with various properties.
And short of being able to give each of you a piece of this leather,
let me show you a little video
just to have a feel - what kind of material is this?
Just think about it.
This material was produced by cells - by us enticing the cells to do it.
The only hocus-pocus that was performed here
is the tanning but nothing else.
This material - you have to take my word - feels like silk.
It has properties
that no industrial leather would ever have -
not saying that the industrial leather is not good.
There are a number of distinguishing features
that this process implies.
First of all,
when we harvest the cells,
the animal, which could be a cow, could be a pig, could be an elephant,
eventually could be even a mammoth
because we're trying to bring back the mammoths -
could be any animal that you could imagine give rise to leather eventually.
So the animal lives after the biopsy.
In principle, we can imagine to use the same animal again,
and that would imply keeping fewer animals,
and that eventually would imply using much less resources.
Furthermore,
this leather that I showed you, this biomaterial is unblemished.
It's uniform.
The animal skin-derived leather is never like that,
because it always contains imperfections,
either because of the barbed wires
or because insect bites or because of abuse.
Ours doesn't.
As a consequence of those imperfections,
the true leather, the industrial leather which derives from the hide of the animal,
is never uniform, it's never homogeneous.
Depending on what your end product is,
you have to source it from the different parts of that hide.
Consequence - you have to discard sometimes 30 to 50% of that material.
This doesn't exist in our process.
We make only what we need or rather the customer needs,
to the same shape that the customer wants -
we generate no waste.
The cells that we use don't produce hair, don't produce flesh.
You have to get rid of those
in the industrial leather production process,
and that requires terrible chemicals, so the process is very toxic.
We don't use those chemicals; we don't have those processes.
The entire tanning process is much more environmentally friendly.
And perhaps, the most important for me as a scientist
is the fact that we can do better than the leather industry.
I mentioned the protein collagen - that's what we're hunting for.
But in our body, there are cells that produce collagen
other than the dermal fibroblasts that reside in our skin.
So with our biopsy,
we can go into any part of the animal, in principle,
and source the cells from other parts of the body,
and those cells will give rise to a different kind of collagen.
Collagen organizes into specialized meshes,
but there are many collagens,
and depending on whether you have a younger or older animal,
again, the organization is different, and the quality is different.
We mimic nature.
But we actually go beyond nature.
We produce material that has been around for thousands of years
in an entirely different way,
in a process that is much more environmentally friendly,
and hopefully, what should I say, it's more humane.
Maybe biofabrication will usher in an era
where we'll be able to produce animal products that we are hunting for,
that we've been using for many, many hundreds of years,
in an entirely different way,
which is very different from the way we've been doing this -
a way that pollutes the environment,
which is very unethical to our animals and has many other adverse properties.
And this is really our goal in the long run.
Now, before I finish,
I would like to return
to the regenerative medicine part of my talk at the beginning.
So obviously, producing human tissues,
the final objective is something like that -
to create the noble organs, the heart, the kidney, the liver.
It could do that, we could live forever -
it's a different question whether you would like to,
but that's what we could do.
Now, I personally don't believe
that we will ever be able to accomplish this.
That sounds bad, especially coming from me.
I don't believe that we'll be able to print the same organs
that we carry in our bodies.
Why?
Those organs are the end result of many millions of years of evolution.
We don't have the time; we can't tinker with nature.
If you really wanted to go through that whole evolutionary process,
you will be dead many times before that.
So that's the bad news.
The good news is that who says that this pump is the best?
Or who says the kidney that we carry in our body
is the best filter?
Nobody.
That's what we have.
But by now, we're fantastic engineers,
we're ingenious engineers,
we're ingenious tissue engineers.
So what I can imagine is that we'll be able
to use this technology to create organs from your own cells,
from the patient's own cells, and that's the important thing,
which will function the same way as this pump,
or will function better than the filter, kidney.
And that's really where I feel
that this technology will eventually converge.
But right now, those tissues can be used for drug development, drug testing,
and that's already a very important contribution.
So in the not-too-long future, if we let our imagination guide us,
maybe we will just walk into a specialized facility,
shed some of our dysfunctional organs,
give up a few million of our still existing and still functioning cells,
and we'll have an organ made to our measure.
(Laughter)
Thank you for your attention.
(Applause)