7.2.25

Episode Transcript

Speaker 1 (00:00):
Welcome. This is Marsha for Radio I, and today I
would be reading National Geographic Magazine dated June twenty twenty five,
which is donated by the publisher as a reminder. RADIOI
is a reading service intended for people who are blind
or have other disabilities that make it difficult to read
printed material. Please join me now for the continuation of

(00:22):
the article I began last time, entitled this Pig Could
Save Your Life by Matthew Cher. The idea was not unprecedented.
For decades, scientists had been transfusing animal blood into or
grafting animal skin onto human patients. The kidney and the
use of immunosuppressants in the human recipients would merely represent

(00:46):
a step up in scale and complexity. A few years later,
Remsma was vindicated when one of his patients survived approximately
nine months with the chimpanzee kidney, a promising feat in
an era when the stakes for patients with failing kidneys
were even higher than they are today. There was no
widespread access to dialysis treatment, and there was no national

(01:10):
donor database for kidney transplants. Euphoria was short lived. In
the nineteen sixties, kidney disease had already reached crisis scale
in the United States, and even if zeno transplantation could
be perfected a big if. Considering twelve of reama's thirteen
patients lasted no more than eight weeks on the chimpanzee organs,

(01:33):
how could scientists possibly secure enough primates A hard to
come by solution simply didn't make sense, says Robert Montgomery,
a transplant specialist at New York University Langone Health and
himself the recipient of a donor heart, he already had
the animal welfare angle. People like Jane Goodall have added

(01:54):
so much to our understanding of how similar we are
to primates, he said. Finally, Montgomery added, there was the
arrival of AIDS, which is believed to have originated in apes.
Having a donor species that is closer to humans on
an evolutionary scale is going to make it easier to
get a good result, Montgomery told me. But by the
same token, it's also easier to pass a pathogen from

(02:17):
a primate to a human than it would be with
another animal, like a pig, say, Despite being notably intelligent creatures,
pigs tend not to be viewed with any particular reverence
by most people eb white, notwithstanding, by one estimate, more
than a billion of the creatures are slaughtered and eaten
by humans every year, and pigs breed with alacrity, typically

(02:41):
twice a year and sometimes three, with litterous averaging eight
to twelve piglets. This is one of the reasons that,
beginning in the nineteen nineties, many researchers in the zeno
field began to gravitate away from primates. But the shift
presented its own unique obstacles, the most vexing of which
was represented by a porcine antigen known as galactose oligos

(03:05):
saccharide or alphagal for short. This antigen, found in pigs,
is not present in the human body, which will attempt
to rid it from the bloodstream by producing antibodies that
bind to the antigen. When this occurs after an organ transplant,
it usually prompts the acute rejection of the donor organ.
Antibiotics and immunosuppressants can help, but not in the long term.

(03:29):
As waves of researchers reluctantly concluded, they realized the need
to remove the alphagal antigen from the pig kidney. A
time consuming process. An efficient solution to this issue was
pioneered in twenty twelve when scientists Emmanuel Charpentier and Jennifer A.
Dudna patented a technology known as Crisper cast nine and

(03:53):
oft used simile likens it to a pair of molecular scissors.
With Crisper, scientists made cuts in humans in human and
animal genetic code, thus replacing disease causing mutations and fundamentally
changing the way genes were expressed in the US and Europe.
Any experimental intervention must pass through two stages before it

(04:14):
is made publicly available. In the preclinical stage, a drug
or surgery is tested in the lab. In the second,
providing the results are acceptable to regulators, research researchers can
move on to humans. In twenty seventeen, a year before
Rick Slayman received a human donor kidney, scientists affiliated with
e Genesis opened a pre clinical trial on several long

(04:38):
tailed macoques that were outfitted with lab modified pig kidneys
informally dubbed knockouts, a nod to the antigens removed via
the gene editing process. One monkey lived nearly three hundred days.
We had a meeting with the FDA, and we basically asked,
what would you need to see in order for us
to move to the next stage? Recalled e e Genesis

(05:00):
CEO Curtis, They gave us a figure of twelve months
survival in a monkey. I was like, well, look, we're
clearly moving in the right direction. But Egenesis was not
alone in its pursuit of FDA approval. Revivicore, a subsidiary
of the biotech firm United Therapeutics, had simultaneously been working
on its own modified porcine kidneys. At a high level,

(05:25):
the engineering methods employed by e Genesis and United Therapeutics,
which is publicly traded and designated as a public benefit corporation,
appear remarkably similar. Scientists at each company start by editing
porcine fetal cells to remove the expression of dangerous antigens,
before cloning the cells via nuclear transfer, a technique that

(05:48):
yields embryos of matching genetic composition. Healthy embryos are then
implanted into female pigs, which give birth to litters of
piglets with identically edited cells. But there the resemblance and
approach end United Therapeutics, for its part, knocks out just
four poresene genes, preferring to utilize a breed of pig

(06:10):
the land race for its fertility and litter size. Conversely,
Egenesis makes sixty different edits to its cells, sixty two
of which are knockouts and even of which and seven
of which are additions from the human genome, and those
cells are different in origin. Egenesis favors relying on the

(06:30):
smaller Eucatan pig breed, whose organs more closely match a
human's in size. In September twenty twenty one, n y
U Langon was granted permission by regulators to transplant a
United Therapeutics edited pig KINDI kidney into a brain dead
human patient. As a brain dead patient is considered legally dead,

(06:53):
the body would be supported by a ventilator during the procedure.
My Gretgomery of n y U Langon was tasked with
carrying out the surgery. I have spent most of my
career trying to increase the number of living organ donors,
Montgomery told me, noting that the annual number of living
human kidney donors has been a flat line for fifteen years,

(07:13):
hovering at six thousand. It was hard not to see
the transplant as a breakthrough. You could sense the enthusiasm.
I felt it too. In October of twenty twenty one,
n Yu Langong went public with the news the Zeno
transplanted kidney had been attached by a network of blood
vessels to the patient's upper leg, where it started to

(07:34):
function immediately creating urine for nearly three days. Just one
major step remained a test on a living patient. Within
hours of Slayman's final informed consent meeting at Winfried William's office,
ears began turning at the Genesis Farming facility. As Bjorn
Petersen watched. The small pig was loaded into the van,

(07:57):
which raced down the road and onto the freeway, douing
cross country journey was a whole logistical dance, Mike Curtiz
told me. Traveling east through the night, the pig reached
a veterinary center in western Massachusetts. There, both its kidneys
were removed by Slayman's surgical team, with euthanasia administered post
pre procedurement. By noon, the organs were packed into a

(08:21):
refrigerated box and placed in the back of a different truck,
who did this time toward Boston. At mass General. Slayman,
who had already been prescribed a strong course of immunosuppressants,
was put under and prepped for surgery while his family
waited anxiously in the waiting area. At one p m.
On March sixteenth, the procedure commenced. From his position in

(08:44):
the operating theater, Williams watched his colleague's Leonardo Riella, Mass
General's medical director of kidney transplantation, Tatsuo Kowai, who had
performed Slayman's original kidney transplant years earlier, had and had
worked with Riella to coordinate the FDA approvals, and Nahel Elias,
surgical director of kidney Transplantation, carried out the procedure. They

(09:08):
all knew the difficulties that Slayman's long struggle with kidney
disease and hypertension would present. His whole vascular anatomy had changed.
Williams said, he had very calcified, very hardened vessels, and
you can't just crack open calcified vessels and make them work.
You've got to find the right anatomic distribution. Plus you

(09:29):
need to remember that mister Slayman was a big guy,
and the vessels that were available for attachment to the
donor kidney were sort of deep within his abdominal cavity.
In the days leading up to the operation, p. S.
Slayman reminded to Haarrish herself how confident her father had
been that the surgery would be a success. When she
entered the recovery sweep that evening, she took her father

(09:50):
by the hand and wept with relief. Although he grasped
the history making meaning of the procedure and the interest
it would inspire in reporters, Slayman told her hospital staff
he'd prefer to stay out at the limelight. Gamely, he
agreed to pose for a few photos with his family
before returning to the house that he shared with his fiancee,
Farren Woolery. Following week was hard. Within a few days

(10:14):
of the surgery, Slayman was diagnosed with symptoms of acute
rejection and treated with what Williams described as the same
anti rejection medication we would use in a garden variety
human transplant. The treatment was effective, but fifty one days
post transplant, Slayman returned once more for an appointment with
Kawai and Riella. The doctors noticed signs of volume depletion.

(10:38):
He was losing more nutrients and fluids than he was
taking in. Sleiman was hooked up to an ivy to
boost fluid volume. Williams told me, and he had a
magnesium infusion to address some low levels. That same day,
Slayman and Woolery left mass Gen General and picked up
groceries near their home in the Massachusetts town of Weymouth.

(10:59):
They made stops two stores. Slayman accompanied his fiancee into
the first one, but begged off when it came to
the second. He didn't feel up to it, he told Woolery.
That night, after eating dinner and watching television together, the
couple went to lie down in the bedroom. Woolery noticed
Slayman's breathing had grown labored and shallow around eleven thirty
p m. Around midnight, Slaman went into cardiac arrest. Woolery

(11:22):
called nine one one, then dialed Williams, who told the
empty crew by phone to take Slayman to the nearest
a muge emergency room. Williams rushed to meet them at
South Shore Hospital in Weymouth, but their combined efforts as
at resuscitation came up short. Slaman passed away in the
early morning of May eleventh, at the age of sixty two.

(11:43):
In the hours after Slamon's death, his family huddled with
Williams at South Shore for a debriefing. Sliman's brother and
fiancee were on hand. Williams explained that it was critical
to understand what had happened to Slayman, giving his relatively
healthy status earlier in the day. After making a call
to Slayman's mother, the family granted permission for an autopsy.

(12:04):
The results, which were published earlier this year, revealed that
the issue had been Slayman's heart, not the kidney. What
we think happened, william said, is that because of his
severe cardiac disease, he had a rhythmia, and he suffered
an a rhythmic event that led to his death. The
tissue of the kidney was healthy, and although there was
residual evidence of the initial rejection symptoms, there was no

(12:28):
acute kidney failure that would have been caused for mister
Slayman's demise. Williams said, bottom line is that the xenograph
was functioning reasonably well. It could be difficult to see
it that way, of course, given that recipients of a
kidney from a diseased human donor can live twelve years,
and recipients of an organ from a living donor up

(12:49):
to two decades. Slayman managed less than two months with
a handful of medical interventions in between, and Lisa Paisano,
who in April twenty twenty four became the second living
patient to receive a modified pig kidney hers from United Therapeutics,
passed away three months after her transplant due to heart issues.
But Montgomery, who led Pizzano's surgery team, offered a useful

(13:13):
reminder patients on the edge of dying already. Patients were
trying to rescue with a brand new technology we're still refining.
Are just not good indicators of how the science will
faire in the long term, Montgomery said, we kind of
set ourselves up with the most difficult scenario. Several days
after Slayman's passing, William's recalt he received an invitation to

(13:34):
speak at his funeral, held at a Baptist church in Milton, Massachusetts.
He wasn't sure how he would be greeted. His mind
traced back to the lingering legacy of the Tuskegee experiments.
When you walk into this kind of congregation, you never
know how you're going to be received, he told me,
because there may be this suspicion, even if it's unspoken,

(13:54):
that they experimented on this individual, like this is what
they do to black people. The church, Williams was joined
by Slayman's entire medical team, and he began his remarks
by introducing Kowai. Immediately, William's fears about his reception vanished.
Before I finished speaking his full name. The entire congregation
gets up and gives us a standing ovation. It was

(14:16):
just unbelievable, the energy. Recounting to me what he told
the pack church, Williams held back his tears. I said,
he'll go down in the pantheon of medical history, he
told me. I wanted them to understand that he had
provided new hope for patients everywhere. In the wake of
Slayman and Pizzano's operations, e Genesis and United Therapeutics, along
with hospitals around the country, fielded a torrent of inquiries

(14:40):
from patients who had spent years on a list for
a human donor kidney. It didn't matter that FDA regulators
were still only authorizing expanded access trials. News of the
transplants had opened the floodgates. People were asking why not me?
Curtis recalled, my health is already declining, why should I
have to wait? Notice, for his part, could only respond

(15:01):
with the truth, Egenesis was working as hard as possible
to get the technology to more patience. I'd say, we
want the same thing, but we want to do this right,
he told me, and doing it right would require approval
for trials on healthier patients. He went on, patients like
Tim Andrews, a former supermarket manager from Concord, New Hampshire.
Andrew Drew's sixty seven, had for two years undergone thrice

(15:26):
weekly dialysis, a process that often took six hours, including
travel in prep time, and left him exhausted and weak.
When I spoke with him about the difficulty of dialysis,
he recalled his appetite disappearing as he dealt with near
constant nausea. He began to stare at the likely reality
of never receiving a human organ and of repeating this
emotionally draining routine for the rest of his life, as

(15:49):
had been the case for Slayman. It was a daunting
thing to try to accept. But last August Andrews was
offered the opportunity to undergo Xeno transplantsy at Mass General
as part of a new three patient FDA approved trial
launched by Egenesis. If he agreed, he'd have the chance
to start over, to have, as he put it, a

(16:11):
second chance. His family was leary. His sister and nurse
warned him about the risks, but he was adamant. This
is not how I want to go out. I want
to do something, Andrews recalls saying, and I knew that
I might die right off, and I said to my
wife and to the Mass General team. If I die
and you learn something, so be it. And if I don't,
then I get to give people hope. That's what I

(16:32):
really wanted. In January, Andrews underwent his transplant, with Kawai
leading the surgery team. Once more, Andrews walked out of
the hospital, beaming, wife Karen at his side. Nothing was certain,
he knew still he had what he'd hoped, a new
lease on life. Every day, he said, is a new day.
When we spoke in March, Andrew's recovery was progressing as planned.

(16:55):
He goes to Planet Fitness twice a week regularly takes
his nine year old German short hair pointer on walks
and helps his wife around the house by vacuuming. If
all continues to go well, he said, next year the
couple will board a plane and visit her relatives in
northern Italy. With his energy returning, Andrews is also trying
to serve as inspiration for the tens of thousands of

(17:17):
people affected by the organ donation crisis. Every Wednesday night,
he meets online with a support group for transplant patients.
They encourage one another on their journeys, and of course
they ask about his poor seeing kidney. I want to
give that hope to everybody else that's on dialysis or
is struggling with kidney disease, he said. This an escape

(17:38):
from dialysis. A whole body reinvigoration is the future for Andrews,
but potentially for dozens of people in the coming years,
should the clinical trials expand to a field of fifty
patients as planned, and both Andrews and Curtis recognize none
of it would be possible without Sleiman and Pizzano, who
proved that the potential of genetic modified kidneys was more

(18:02):
than hypothetical in a real solution worth pursuing to get here.
We owe so much to brave people like mister Slayman,
and to all scientists on whose shoulders we stand. Kurtis
told me, we have been fortunate to enter the field
when we have because we're able to leverage decades of
progress and research and integrate it all into making this
thing a reality. You have to kind of pinch yourself,

(18:24):
but here we are proud to design a life saving kidney.
Placing a pig's kidney inside a human patient is more
complicated than merely swapping one organ for another. For the
biotechnology company, e genesis process begins by genetically modifying the
embryo of a Yucatan pig so or grow kidneys that
will be accepted by the human body. Here's how it's done.

(18:48):
One evaluate a tissue sample. A specimen from the ear
of a Yucatan pig is carefully reviewed or sequenced to
ensure there are no issues that will interfere with the
gene editing process. Two delete problematic pig genes using the
gene editing technology Crisper. E Genesis scientists must alter the

(19:08):
tissue sample to prevent the spread of viral disease. And
potential organ rejection. This means removing four pig specific genes
three make it more human. Scientists then insert seven human
genes into the sample's DNA that will protect the future
kidney from inflammation, cell damage, and coagulation, and also trick

(19:29):
the human immune system into accepting the foreign organ. Four
insert the modified DNA. The edited DNA is then fused
with a nuclei of fetal pig cells. Scientists implant these
developing embryos into a sow that will give birth to
piglets capable of growing human ready kidneys. Five, harvest the

(19:52):
organ and transplant into patient. Whence the piglets reach maturity,
their kidneys can be harvested and prepared for transplant. After surgery,
patients must still take immunosuppressive drugs to prevent human organ rejection.
Beyond kidneys, pigs are ideal candidates for xeno transplantation because
their organs are similar in size to ours and have

(20:15):
a similar anatomy and function. Research is under way to
determine which body parts from pigs could be most useful
to humans a kidney crisis. More people than ever need
a kidney transplant, but in twenty twenty four is thirty
percent of patients on the waiting list received one. Doctors
hope Zeno transplantation could soon address that unmet need for

(20:37):
more kidneys and endless weight. Patients who are able to
immediately receive a kidney from a human donor are often
required to go through painful and tiring dialysis treatments to
stay alive. Next article Oases on the Brink by Tristan
mc connell. Across the world, hundreds of millions of people
have relied for centuries on desert wetlands that are now vanishing.

(21:01):
In southern Morocca, one community is blending ancient knowledge with
modern innovation to protect the oasis. Driving south out of
the Atlas Mountains into Morocco's Draw Valley, travelers find that
the landscape becomes increasingly stark until the paved National Highway
vanishes into the desert. At the oasis town of Mohammed

(21:22):
el Ghislane, the sometimes known as the gateway to the Sahara,
Ahmed and its surrounding villages are home to about sixty
one hundred people for generations. The settlement has straddled the
Dara River, with wispy tamarisk trees lining the road on
the north bank of the river and palm plantations spreading
out to the south. But today the concrete bridge built

(21:45):
to span the water rises over a dry riverbed of
sand and gravel. Tourists still come to Mohamed, drawn to
camel tracks, camping and sand boarding. They arrive by the
bus load and make their way to hotels that offer
swimming pools and massages. A leam spy, fifty five tall
and bespectacled with dark gray flecked hair, was borne in

(22:05):
the town like a lot of residence. He remembers a
different Mohmet, greener lusher. When he was a kid, he
herd a live stock beneath the dense shade of thick
groves of palm trees and fished in the draw, Morocco's
longest river as it wound lazily through town. In the
decades since, he has watched the oasis shrivel as the
rain has all but stopped and the river has dried up.

(22:28):
The thick forests of dap palms have withered and thinned,
and the fields of fruit and olive trees have produced
less and less each year. Most young people have escaped
for a better life elsewhere, leaving houses in entire neighborhoods
to be swallowed by the encrossed croaching dunes. When there
is no water, nothing green, the sand becomes very strong,
a very fast enemy, says Spy. It takes a lot

(22:50):
of land. The desert is pressing in from every direction.
According to Spy, the outer edge of the oasis moves
inward by more than three hundred feet eet each year.
Sometimes Sabai worries that he might be witnessing the end
of the oasis altogether, and with it an ancient ecosystem
and the nomadic culture and traditions it enables that he

(23:11):
holds deer. For thousands of years, people have lived and
thried in oayses, developing a complex agricultural system finely calibrated
to the harsh desert environment with its water scarcity and
ecological fragility. By some measurements, owases occupied seven hundred forty
thousand square miles worldwide, roughly three times the area of

(23:32):
Texas and in North Africa, and Asians sustain an estimated
one hundred fifty million pupil. In Morocco, oases are home
to one million pupil. The stresses of contemporary climate change
are accelerating with increasing aridity, temperatures, and the desertification, as
well as destructive floods and wildfires. Yet, Sabai is an

(23:56):
optimist steeped in nomadic culture, and he believes that owaysies
contain the seeds of their own salvation. What is an
oasis an imagined place, a mythical one, an isolated palm
fringed pool in the desert, a place of safety, somewhere
desperate travelers might find relief or dismay if the oasis

(24:16):
turns out to be a mirage. Ecologically, it is simply
an area made fertile by a water source in an
otherwise harsh and arid environment. But human ingenuity has transformed
oases into complex civilizations. Ten thousand years ago, northern Africa
was hammered by strong monsoon rains and the Sahara was burdened.

(24:36):
With the climate gradually shifted and the grasslands and rivers
dried up. In the newly unforgiving desert landscape. Water was scarce.
Where people found it, they exploited it and created pockets
of habitable land that made life not just possible, with
prosterus providing homes and livelihoods to many thousands. Radiocarbon dated
barley and wheat grains, as well as millstones used to

(24:59):
grind flower show that oases were already developing in the
Draw Valley during the fifth century. As oasis grew, so
too did Saharan trade. Date palms. The hallmark species of
the oasis are drought and heat resistant and grow steadily
in the desert wherever there's water close to the surface,
but it takes huge amount of labor and engineering to

(25:22):
successfully cultivate them. These costs were in part met by
the salt, gold and textile traders who plied the caravan
roots between Marrakesh and Timbuctu. Oases were a place for
them to rest and restock before their next expedition. As
Spy puts it, you can't be a nomad all the time,
just moving everywhere. You need to stop relax. The essential

(25:43):
ingredients of the oasis are date palms and people, and
neither flourishes without the other. The thick fronds of the
date palms crown provide a shady canopy beneath which other
species can grow protected from the punishing sun. Scientists have
described the date palm as a keystone species for the
ingenious three tiered agricultural ecosystem it anchors. The tree produces

(26:07):
valuable dates, and the humid, temperature controlled microclimate beneath the
den's overstory fosters other crops such as fruit, olive, and
hannah trees. At ground level, beans, wheat, barley, and alfalfa
grow protected from the wind and sand by the palm's
tough trunks. Mohammed at El Moktar, professor of plant physiology

(26:30):
and biotechnology at Hassan, the Second University in Casablanca, who
has studied the impact of climate change on oasis ecosystems,
describes the date palm as the umbrella beneath which all
else thrives. If we want to sustain this structure in
the oasis, we have to sustain the date palm. He says.

(26:50):
Oases worked, in other words, because they stayed in balance.
Rainfall in this part of Morocco was always sparse, but
still the drawer was filled with snowmelt and rain water
that flowed more than eleven thousand feet down from the
peaks of the High Atlas Mountains. Farming communities work together
to dig and maintain geometric networks of irrigation channels to

(27:11):
siphon river water into the palm plantations. They use stone,
mud bricks and rammed earth to build warnlike fortified homes
and villages, nonsksars and casbahs, and expanded their agricultural lands
into the increasingly irrigated desert. But climate change has devastated
many oases and its only expected to get worse. Temperatures

(27:34):
in Morocco are projected to rise by as much as
nine degrees fahrenheit by the end of the century and
rainfall to be reduced by thirty to fifty percent. Extreme
flooding is on the rise and government figures show that
around ten thousand palm trees burned every year in wildfires.
This concludes readings from National Geographic Magazine for to day.

(27:55):
The reader has been Marsha. Thank you for listening, Keep
on listing and have a great day.