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This Heart is Not Human

A pig heart in a human? Before this year, a surgery like this seemed unlikely, but over 50 years of innovations have made it possible. WIRED spoke with Dr. Brandon Guenthart to understand exactly how this surgery works, and why the future of surgery might look similar. Director: Maya Dangerfield Director of Photography: Tim Neff Editor: Josh Pullar Expert: Dr. Brandon Guenthart Line Producer: Joseph Buscemi Associate Producer: Samantha Vélez Production Manager: Eric Martinez Production Coordinator: Fernando Davila Post Production Supervisor: Alexa Deutsch Post Production Coordinator: Ian Bryant Supervising Editor: Doug Larsen Assistant Editor: Andy Morell

Released on 10/13/2022

Transcript

[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 evalsuation.

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.

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