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Things aren't what they used to be.
First we changed the planet to suit our needs.
And now we're about to rebuild ourselves from the inside out.
A new science, barely a decade old, is creating man-made tissues and organs.
Replacement body parts coming soon from a laboratory near you.
Transplant medicine is in deep trouble.
There aren't enough organs to go around.
Donna Robinson found out the hard way four years ago.
Though desperately ill, she had to wait months for a liver transplant.
I became extremely depressed, very depressed and agitated and they, they medicated me for
a while to keep me calm because I, at the time I had a 12 year old.
And I was afraid, wait a minute, sorry.
It's the first thing I thought it was.
I wanted to see my daughter graduate high school and, oh man, I'm screwing this up
for you.
After an agonising wait, a healthy liver was found.
It came from an 18 year old crash victim.
After eight hours of surgery, Donna had a new liver.
She knows she was very lucky.
We say to people that my transplant, my marriage and my child are my greatest gifts.
I just, I'm so grateful, I can't even express to you how grateful I am about it.
Donna was more fortunate than most.
Every year hundreds of thousands of people around the world are in desperate need of
a replacement liver, heart or kidney.
Usually there's organs for barely one in ten of them.
Many of the other people die waiting.
One possible solution to the crisis is to use organs from animals like baboons and pigs.
Strange numbers could easily be bred, and while there are some major ethical concerns,
some researchers felt that it was only a matter of time before baboon heart transplants might
become routine.
Several much publicised operations showed that ethics weren't the only obstacles.
Tiny baby Faye lived for just 20 days after getting a baboon heart before a massive rejection
reaction set in.
That was 1984.
To this day, no one has survived more than 70 days with an organ transplanted from another
species.
I began doing liver transplants in children in 1983 and 84, and in the children in that
era, the organ shortage was really much more acute, and you could see the future by looking
at what was happening to the children.
Across the river at MIT, Bob Langer was heading towards a very different future.
The world of chemical engineering, but a chance meeting dramatically changed his path.
Both Jay and I met back in 1977.
We worked in the same lab.
I was a postdoctoral fellow and he was a surgical fellow, and we got to know each other then.
And several years later, when he was on the staff of Boston Children's Hospital, he talked
to me about some of the problems he faced as a transplant surgeon, and together we talked
about how we might try to create solutions to those problems.
Jay and I thought in the early 1980s that it might be possible to engineer organs, and
so we came up with this general idea of could we combine plastics, I'd already done a lot
of work with plastics, and cells.
The extension was really, okay, if you can build a thin layer of skin, maybe you could
build a whole liver or a whole kidney or a whole heart, and other people thought that
was a fairly big leap, but in my younger, more naive years, I thought that it seemed
like a perfectly logical step.
It was a breathtaking concept, but in principle, there was a clear way to proceed.
First, as with any solid construction, they needed scaffolding, a strong frame to support
the tissue and give it form.
Then they'd have to work out what kinds of cells and other raw materials they'd need,
depending on what organ they were building.
In 1992, one of Bob Langer's research team invented a machine that would make it all
possible.
Michael Cima built what was in effect a 3D printer, capable of turning intricate computer
designs into three-dimensional structures.
The best part was that you could make them from biodegradable polymers, the same material
used in surgical sutures.
I mean, the idea is reminiscent of Star Trek or something like that, where you just press
a button and the machine pops out apart, and ultimately, that's what we want this process
to be, is as close to that as we can get.
A battery of tests suggested that biodegradable scaffolds made with the 3D printer should
make perfect growing platforms, but it wasn't until Jay Vikanti's team added the cells
that they would discover that the technique really worked.
The cells thrived in their new home.
New engineering had been born.
Soon, labs everywhere began their own experiments, some with a touch of Frankenstein.
Taking their design from the ear of a Massachusetts boy, one team fashioned this polymer scaffold.
For ethical reasons, they couldn't implant it under human skin, they chose a hairless
mouse instead.
Suddenly, tissue engineering had everyone's attention.
The scientists responsible ducked for cover, but many others worried that it could all
spin out of control.
At the University of Toronto, Michael Sefton decided to seize the moment.
He'd been trying to develop novel solutions to the problem of tissue rejection, but if
organs could be built from scratch in the laboratory, then rejection might not even
be an issue.
Question was, who was actually going to build them?
No single research group could possibly have all the expertise to build a living heart,
for example.
Without a coordinated plan, the whole idea might die before it even began.
Michael contacted Jay Vacanti, Bob Langer and others in the field, and proposed they
set up the Life Initiative, an international research consortium united by a common goal
to build a human heart, estimated cost $10 billion.
Our goal is to be able to have a heart ready for clinical testing about a decade from now,
assuming we get all the money in at the right time or whatever, but at that kind of time
frame, not 50 years and not five years.
Now the game was on.
The Life Initiative sent a clear message that scientists were serious about building replacement
body parts.
For the first time, people began to realise where this research might lead.
One of the questions I've had, and I'm not really sure I know the answer to it, is well,
what if people want a Michael Jordan heart, you know, an enhanced heart, a high-performance
heart?
Would it be okay to give them one?
And I don't know the answer to that.
To build an organ, you need a reliable source of cells.
That's no simple matter.
The cells in our bodies won't grow on demand.
They have their own agendas.
When we're growing up, many of them are madly multiplying.
But some, like muscle and nerve cells, stop dividing before we're even born.
By the time we're adults, only a handful of cell types, like skin, blood, cartilage and
bone, retain the ability to reproduce.
That makes it extremely difficult to grow them in the laboratory.
The trick is to make cells believe that they're not in some glass dish, but safe and warm
inside a growing embryo.
It's taken years to figure out how to woodwink them.
The breakthrough came when researchers realised that cells speak a complex language of chemical
signals.
Give them the right signal and they'll do what you want.
Get it wrong and they'll run amuck and turn cancerous or die.
In Bob Langer's Boston lab, Lisa Freed and Gordana Vunjak-Nivakovic had more success
than most at speaking the language of the cells.
They also had a secret weapon, a machine called a bioreactor.
The bioreactor is a humidity crib for cells.
It not only provides them with life's essentials, but by gently spinning, it ensures that nourishment
penetrates to the heart of even the thickest clump.
Gordana and Lisa found just the right chemical signals to get cartilage growing on a biodegradable
scaffold.
They ended up with pieces that were as thick as knee cartilage.
Then in July this year, they succeeded in growing one of the most difficult but desirable
of cells, heart muscle.
In here you might be able to appreciate the cells which are attached to scaffolds that
are held shish kebab style on a needle in here.
The heart muscle cells did so well, they even formed electrical connections with each other,
just like in the real heart.
But how did such bioartificial tissues measure up against the real thing?
It was more than likely that forces like gravity and the subtle pressures that exist inside
a living body influenced their strength.
They had to know for sure.
A bioreactor with cartilage cells was sent into orbit in the Mir space station.
After four months as guests of the Soviet space program, the cells were substantially
smaller and the cartilage itself brittle and weak.
The message was clear.
To grow big and strong like the human body itself, artificial tissues need exercise.
They give their best when pushed and stretched.
In Durham, North Carolina, a young anaesthesiologist named Laura Nicholson would have an opportunity
to put this discovery to the test.
Her interest was not in major organs but the blood vessels needed for heart bypass surgery.
You really can only replace it with one of your own vessels, in other words we have to
rob Peter to pay Paul.
If you need a new artery we have to take either an artery from somewhere else or one of your
own veins and patients who need their arteries replaced in their heart or their legs typically
need this procedure done more than once.
There's only so much vein that you can rob from yourself before you run out and then
these patients face either no therapy for their heart disease or amputation.
Using cells from a pig, Laura grew arteries in a bioreactor.
She made an important modification, a pump that delivered a strong pulse like a heartbeat.
We found that when we pulse arteries as they're growing in these bioreactors they tend to
develop into an artery that's stronger, that has more collagen, more of the strong protein
that holds tissues together.
Laura had enough faith in the engineered arteries to put them to the ultimate test.
She re-implanted them into the pigs whose cells she'd used.
That was exciting because nobody had really shown that it was even possible to take cells
from an animal, grow that new artery tissue and then put it back in and have it work.
That was really the first time that that had been successful.
There was still a serious problem.
All of the engineering successes so far had used cells that were very specialised.
It severely limited what you could do with them.
Some people believed it might be possible to find younger cells whose fate hadn't yet
been determined.
Cells that in the laboratory might be persuaded to become anything at all.
But where could you find such cells?
That clue came from looking at what happens to each and every one of us.
We start out as a twinkling in our mother's eye, a single fertilised egg, then somehow
that one cell full of promise becomes the complexity that is a human being.
If there are cells within us that can equally turn into blood or bone, then they must surely
exist in the earliest moments of our lives.
In November 1998, two teams, one in Baltimore, the other in Wisconsin, independently announced
that they had found these so-called human embryonic stem cells.
It was a staggering discovery.
These right here are the living human pluripotent stem cells, which I'll get ready to show
you now.
What you'll be able to notice is that these cells grow as tightly packed colonies, and
one of those colonies can be seen right there.
If this living ball is allowed to develop, it can change into something quite bizarre.
Some cells spontaneously become nerves, others turn into blood vessels or digestive cells.
In fact, they can take on any one of 200 different identities.
It seemed the answer to the tissue engineer's prayers, an endless supply of whatever cells
they needed.
But there was a catch.
The stem cells then come from highly controversial sources, to say the least.
Created human fetal tissue, non-living, and deep frozen human embryos obtained from an
in-vitro fertilisation clinic.
Just one week after the announcements, President Clinton expressed his deep concern.
The US Congress demanded an explanation.
Since 1994, there had been a ban on the federal funding of any research that used human embryonic
tissue.
Although aborted fetal tissue doesn't fall into that category, both research teams were
in fact funded privately by the same company.
Nevertheless, Congress wanted an assurance that the embryonic stem cell research was
not manufacturing human embryos in the laboratory.
These cells in and of themselves cannot form an embryo.
When you grow them in a dish, you're not forming little embryos or anything.
These are just tissues, OK?
They are not organised in any fashion to resemble an embryo.
The furor did not die down.
Some congressmen demanded that all stem cell research be banned outright.
John Gerhardt was unmoved.
He still believes his research is perfectly ethical and that there's no harm in using
aborted fetal tissue.
We took the position of utilising fetal tissue.
The option here then is, well, can you use this tissue that's going to be thrown away
for benefit?
And when you put it in that type of a framework, to me, I don't have a problem with this whatever.
But just down the road from Johns Hopkins, a small biotechnology company called Osiris
Therapeutics had found a way to reap the benefits of stem cell technology without getting embroiled
in the ethical battle.
The stem cells they use aren't from embryos, but from the bone marrow of adults.
Osiris scientists have worked out how to grow masses of these cells and then convert into
own cartilage fat cells.
They're not using them to build new organs.
Instead, they plan to inject the cells into parts of the body that are damaged and let
them repair the wounds.
The beauty of this technique is that it uses the patient's own cells, so tissue rejection
isn't an issue.
And we're just recovering some of these cells from individuals and using them to regenerate
tissues that normally don't regenerate very quickly or very well, such as the joint cartilage.
And this way we can try to get the joint cartilage, for example, in the knee or the hip to repair
itself and regenerate as quickly as skin will heal on a cut.
It's clearly a multi-billion dollar industry, especially as society ages and as the average
age of the population increases in Western society, we find that more of these diseases
like osteoporosis and arthritis become very, very important.
Osiris Therapeutics is poised to make a killing.
They've recently discovered a way to repair a damaged heart without surgery.
In this microscope view, green indicates the heart muscle of a mouse.
It's damaged.
The red streaks are regenerating heart cells that have been injected directly into the
heart.
Over just two weeks, they repair the damage and become a permanent part of the heart.
Of course, Osiris isn't the only company in the business of repairing life.
Others have already created bio-artificial ligaments, tendons and skin.
Some of these products are already saving lives in American hospitals.
But perhaps the greatest challenge for any tissue engineering company is having command
of enough skills to create a complete product.
With each new breakthrough, the race to acquire portfolios of patents has accelerated.
Without a doubt, this company in Menlo Park, California is ahead of the pack.
Not only have Geron invested heavily in controversial embryonic stem cell research, they've recently
acquired a controlling interest in the Roslin Institute, the Scottish laboratory that cloned
Dolly the Sheep.
I think one of the things that we're trying to do is accumulate a mass of technology that
will allow us to actually make regenerative medicine a reality.
A crucial step towards making that happen, they believe, is the control of a powerful
substance called telomerase.
It's been called the cellular fountain of youth.
If you look at what happens when you put the telomerase gene into cells prior to the aging
process, they're much smaller and telomerase was able to prevent their deterioration in
culture.
They're immortal by every possible mechanism we can look at right now.
Amazing stuff.
If you can keep a dish of cells forever young, imagine the possibilities, extending the lives
of tissues and organs and maybe even people.
Couple that with cloning and stem cell technology and you've got some powerful medicine.
Maybe too powerful.
Some worry that such far-reaching technology might end up in control of a mere handful
of biotech barons.
Others say that's just not possible.
I think it's going to, in the end, involve a pretty large group of companies, if you
will, or universities who ever own these patents.
Nothing is going to be simple.
It's not going to be held by one individual.
I guess I'm not as optimistic that it's going to come to me.
I don't think so, this big thing.
It's going to turn out to be a big group effort.
There are still many problems to be solved.
After all, these technologies are still in their infancy, but there have been enough
breakthroughs in recent times to glimpse the brave new world they're creating.
All of those put together are going to pave the way for really growing all sorts of tissues
in the next 10 to 20 years.
It will be a very different landscape.
I think it's a problem of engineering as well as biologic science, but there's nothing
that says to me it is not doable.
I think we're driven by two things.
One, the enormous amount of good that could happen if we're successful, and two, the
scientific challenge that science will understand as we go down that path, which we hope will
be useful to many people in many different areas.
In some ways, the technology has developed faster than I even thought it would, so that
now we're looking at the concept of tissue engineering, that is something that is astounding
to me.
I'm going to see her graduate October 22nd, and I didn't think I was going to see a high
school graduation, so I'm very, very grateful.
With the flood of new discoveries and the adventurous spirit so apparent in research
labs, we are going to see a major shift in the way we treat many diseases.
Much of today's experimental techniques becomes the standard procedure tomorrow is difficult
to predict, but transplant medicine will never be the same.
Thank you very much.
You