- [Narrator] These surgeons are putting a pig heart
into a human.
Before this year,
these types of surgeries seemed impossible.
How his heart ended up here, is a complicated journey.
Over 50 years of innovations made it possible.
And it's all in an attempt to solve a major problem.
Not enough organs for transplantation.
- In the US alone, it's estimated
that one patient dies every hour, as they wait.
- [Narrator] which takes us back to here.
To an operating room at NYU.
Where a genetically-modified pig heart beats inside
of a deceased donor, and shows no signs of early rejection.
- So not only did it not reject,
but it actually did its job.
The steps happening now at NYU,
have really shown to the scientific community
that it's feasible.
It's possible to transplant a modified pig organ
into a human.
- [Narrator] "Wired" spoke with Dr. Brandon Guenthart,
to understand how exactly the surgery works,
and why the future of surgery might look similar.
- For decades, scientists and surgeons
have been struggling to come up with solutions
for a huge problem that we have.
And that's the shortage of donor organs.
Every organ, unfortunately, that's donated, cannot be used.
We have to be picky.
It has to have good function.
It has to have appropriate size.
It's believed that they're underrepresented
of the actual need, by a factor of at least 10.
So in other words, for every 10 patients
that actually need an organ,
we think only about five actually make it
to medical evaluation.
And of those, only one will get on the list.
- [Narrator] Xenotransplantation is the transfer,
or transplantation of cells, tissues, or organs
from one species to another.
It's a field that has a long history
of experimentation and setbacks.
However, the last few years,
there have been huge leaps forward.
Pioneering heart and kidney transplants at NYU,
David Bennett received the world's first
genetically-modified pig heart.
The first peer-reviewed research
of pig-to-human kidney transplantation was published.
And this summer, surgeons at NYU Langone
transplanted genetically-modified pig hearts
into deceased donors maintained on ventilators.
- It was done first in a deceased patient,
really to prove safety.
It's really landmark work, but there's still a lot to know.
- [Narrator] What we're seeing here is the final step.
To understand how xenotransplantation works,
we need to go to a lab like this one.
The success of xenotransplantation owes a lot
to improvements in the field's knowledge of immunology,
better testing, better knowledge of tissue
and organ compatibility,
and better immunosuppressive regimes,
have made organ transplants increasingly effective.
It's also led scientists to an ideal organ partner.
- Initially, most of the early attempts
at xenotransplantation were done in primates.
For that kind of logical step of, well,
they're closest to us. We should try that first.
This includes a very famous case of Baby Fae,
who was a newborn in the 1980s that received a baboon's
heart.
Unfortunately, she only lived about 20 days.
Since that time, pigs have really emerged
as the ideal donor source, for several reasons.
Pigs are very similar in anatomical size, function,
physiology and immunology.
Pigs, fortunately, grow fairly rapidly,
and they're usually adult size by six to nine months of age.
Crispr/Cas Nine, is one tool in a family of tools
that has really changed the game in terms of our ability
to manipulate and edit genes.
You can think of it as a pair of scissors,
and it's able to go in and make cuts,
and take pieces of that string or genes out.
And, at the same time,
also insert genes into the genetic code.
- [Narrator] The technology is an important tool
that solved a huge hurdle.
How to bridge 80 million years of evolutionary differences.
- Right now, all of the cases that have been accomplished
have been done with the 10 edit modified pig.
So for instance, they've deleted a gene
that encodes for our carbohydrate marker
on the surface of pig cells and organs.
You can think of that as a marker on these organs
and cells that tells the world that this is from a pig.
Other genes that were added were human genes,
and genes that make the organ better apt
at dealing with coagulation and inflammation and swelling,
and make it more like us.
Ultimately, without these modifications,
organs would succumb to rejection, and fail.
What we found experimentally,
even with the highest levels of immunosuppression,
essentially almost turning off the human immune system,
these organs will ultimately fail.
And so they do need the modification
and they need to be more like us.
- [Narrator] Once the genes are edited and the organs grown,
the next step is matching with a human donor.
- Most patients will not be eligible for a human transplant.
Otherwise, that's what they would get.
Second, they need to be strong enough to survive,
and make it through a long, complex surgery.
We also want their other organs to be functioning well,
so that they can recover well after surgery.
And then most importantly,
it takes an individual that's brave enough to agree
to what still is an experimental procedure,
and understand the risks,
but potential benefits that it would carry.
- [Narrator] Which leads us back to here.
This surgery is a combination of decades of research
in multiple fields.
The goals of the surgery were two-fold.
To monitor for early signs of organ rejection,
and to see if the heart could function
without additional support.
In order for xenotransplantation
to revolutionize our transplant system,
these organs have to function the same,
or even better than human organs.
- So the idea of xenotransplant would be
that we'd have younger, stronger, better matched organs.
And our goal would be that they would last as long,
or longer than human organs.
The recent advances we've made in xenotransplant
has shown that in the short term,
these organs function and they're safe.
But what we don't know quite yet, is the longevity.
Will they last for days, months, years, or decades?
And as we saw in the case of David Bennett,
incredibly promising,
but there's still many obstacles and barriers
yet to overcome.
- [Narrator] Rather than transferring entire organs,
Dr. Guenthart's lab at Stanford,
along with collaborators at Vanderbilt and Columbia,
uses pig organs to revive
and recover damaged human organs for transplant.
- My work has really focused on a different approach.
So rather than taking whole organs and transplanting them,
we use the whole pig as a support system,
where we take damaged human organs,
many of which we've talked about
that just aren't able to be used and offered to patients,
and we connect them to a humanized pig,
so that that humanized pig can provide all
of the multisystem support to allow recovery
in the human organ.
And provide them, whether it's hours or days,
time to recover, and allow us to intervene on that organ
to improve it, and get it to a point
where we can transplant that human organ into a patient.
I think early on initially, the kidneys, livers,
and heart will be the first organs to successfully
be used in xenotransplantation.
Given their favorable immune profile,
we need less immunosuppression, less drugs,
to drive down our own immune system.
Conversely, I think lungs will probably be the last.
Every breath we take, those organs are in contact
with the outside environment.
Which makes them a very difficult organ to transplant.
- [Narrator] The reason xenotransplant successes
are all steps towards clinical trials,
which are large scale research studies
that are rigorously vetted by the FDA.
- Organ transplant is really meant
to provide patients decades of life, not just years or days.
And so we want the work in xenotransplant to mimic that,
and to provide that same longevity.
I am excited.
I think over the next five to 10 years,
with xenotransplantation, what we're gonna see is
that more organs are available.
And that more transplants are happening.
There's a lot of work that goes into this,
and I think the whole scientific community around the world,
I think has now seen the promise of xenotransplant,
and is invested in making it move forward.