7.2.25

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 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 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, 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 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 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

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

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. 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 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 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 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 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, 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

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

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 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, 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, 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 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, 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 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 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 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 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

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 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. 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. 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 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. 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.

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 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

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

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 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, 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 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 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 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 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

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 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 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. 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 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

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 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, 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. 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 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 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 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 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

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. 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 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 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 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.

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 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 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 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 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 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. 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 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

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 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 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 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.

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

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 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. The reader has been Marsha. Thank you for listening, Keep on listing and have a great day.