{"id":596773,"date":"2023-01-12T05:48:53","date_gmt":"2023-01-12T11:48:53","guid":{"rendered":"https:\/\/news.sellorbuyhomefast.com\/index.php\/2023\/01\/12\/the-entrepreneur-dreaming-of-a-factory-of-unlimited-organs\/"},"modified":"2023-01-12T05:48:53","modified_gmt":"2023-01-12T11:48:53","slug":"the-entrepreneur-dreaming-of-a-factory-of-unlimited-organs","status":"publish","type":"post","link":"https:\/\/newsycanuse.com\/index.php\/2023\/01\/12\/the-entrepreneur-dreaming-of-a-factory-of-unlimited-organs\/","title":{"rendered":"The entrepreneur dreaming of a factory of unlimited organs"},"content":{"rendered":"
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Organs on demand is one of MIT Technology Review\u2019s 10 Breakthrough Technologies of 2023. Explore the rest of the list here.<\/a><\/em><\/p>\n

I met the entrepreneur Martine Rothblatt for the first time at a meeting at West Point in 2015 that was dedicated to exploring how technology might expand the supply of organs for transplant. At any given time, the US transplant waiting list is about 100,000 people long. Even with a record 41,356 transplants last year in the US, 6,897 people died while waiting. Many thousands more never made the list at all.\u00a0<\/p>\n<\/p><\/div>\n

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Rothblatt arrived at West Point by helicopter, powering down over the Hudson River. It was an arrival suitable for a president, but it also brought to mind the delivery of an organ packed in dry ice, arriving somewhere just in time to save a person\u2019s life. I later learned that Rothblatt, an avid pilot with a flying exploit registered by Guinness World Records, had been at the controls herself.\u00a0<\/p>\n

Rothblatt\u2019s dramatic personal story was already well known. She had been a successful satellite entrepreneur, but after her daughter Jenesis was diagnosed with a fatal lung disease, she had started a biotechnology company, United Therapeutics. Drugs like the one that United developed are now keeping many patients like Jenesis alive. But she might eventually need a lung transplant. Rothblatt therefore had set out to solve that problem too, using technology to create what she calls an \u201cunlimited supply of transplantable organs.\u201d<\/p>\n

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Lawyer and entrepreneur Martine Rothblatt in a 2014 photo.<\/figcaption>

PETER HAPAK\/TRUNK ARCHIVE<\/p>\n<\/figure><\/div>\n

The entrepreneur explained her plans with the help of an architect\u2019s rendering of an organ farm set on a lush green lawn, its tube-like sections connected whimsically in a snowflake pattern. Solar panels dotted the roofs, and there were landing pads for electric drones. The structure would house a herd of a thousand genetically modified pigs, living in strict germ-free conditions. There would be a surgical theater and veterinarians to put the pigs to sleep before cutting out their hearts, kidneys, and lungs. These lifesaving organs\u2014designed to be compatible with human bodies\u2014would be loaded into electric copters and whisked to transplant centers.\u00a0<\/p>\n

Back then, Rothblatt\u2019s vision seemed not only impossible but \u201cphantasmagoric,\u201d as she has called it. But in the last year it has come several steps closer to reality. In September 2021, a surgeon in New York connected a kidney<\/a> from a genetically engineered pig developed by Rothblatt\u2019s company to a brain-dead person\u2014an experiment to see whether the kidney survived. It did. Since then, US doctors have attempted another six pig-to-human transplants.<\/p>\n

The most dramatic of these, and the only one in a living person, was a 2022 case in Maryland, where a 57-year-old man with heart failure lived two months with a pig heart supplied by Rothblatt\u2019s company. The surgeon, Bartley Griffith, said it was \u201cquite amazing\u201d to be able to converse with a man with a pig\u2019s heart beating in his chest. The patient eventually died, but the experiment nonetheless demonstrated the first life-sustaining pig-to-human organ transplant. According to United, formal trials of pig organs could get underway in 2024.<\/p>\n

At the center of all this is Rothblatt, a lawyer with a PhD in medical ethics whom New York magazine dubbed<\/a> the \u201cTrans-Everything CEO.\u201d That isn\u2019t only because she changed her gender from male to female in midlife, as she writes in her book From Transgender to Transhuman<\/em>. She\u2019s also a prolific philosopher on the ethics of the future who has advocated civil rights for computer programs<\/a>, compared the traditional division of the sexes to racial apartheid, and founded a transhumanist religion, Terasem<\/a>, which holds that \u201cdeath is optional and God is technological.\u201d She is a frank proponent of human immortality, whether it\u2019s achieved by creating software versions of living people or, perhaps, by replacing their organs as they age.<\/p>\n

Since the pig organ transplants garnered front-page headlines, Rothblatt has been on a tour of medical meetings, taking the podium to describe the work. But she has rebuffed calls from journalists, including me. The reason: \u201cI promised myself no more interviews until I accomplished something I felt worthy of one,\u201d she wrote in an email. She included a list of the further successes she is aiming for. These include keeping a pig heart beating for three months in a patient, saving a person\u2019s life with a pig kidney, or keeping any animal alive with a 3D-printed lung, another technology United is developing.<\/p>\n

The next big step for pig organs will be an organized clinical trial to prove they save lives consistently. United and two competitors, eGenesis and Makana Therapeutics, which have their own pigs, are all in consultation with the US Food and Drug Administration about how to conduct such a trial. Kidney transplants are likely to be first.<\/p>\n<\/p><\/div>\n

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\u201cMany people are not on the list because of the scarcity of organs. Only the most ideal patients get listed.\u201d<\/strong><\/p>\n

Robert Montgomery<\/cite><\/p><\/blockquote>\n

Before the larger human trials can begin, companies and doctors say, the FDA is asking them to perform one more series of experiments on monkeys. The agency is looking for \u201cconsistent\u201d survival of animals for six months or more, and it is requiring that the pigs be raised in special germ-free facilities. \u201cIf you don\u2019t have those two things, it\u2019s going to be a hard stop,\u201d says Joseph Tector, a surgeon at the University of Miami and the founder of Makana.\u00a0<\/p>\n

Which company or hospital will start a trial first isn\u2019t clear. Tector says the atmosphere of competition is kept in check by the risk of missteps. Just two or three failed transplants could doom a program. \u201cDo we want to do the first trial? Sure we do. But it\u2019s really, really, important that we don\u2019t treat this like a race,\u201d he says. \u201cIt\u2019s not the America\u2019s Cup.\u201d\u00a0<\/p>\n

Maybe not, but leading transplant centers are jockeying to be part of the trials and help make history. \u201cIt\u2019s \u2018Who will be the astronauts?\u2019\u201d says Robert Montgomery, the New York University surgeon who carried out the first transplant of a pig kidney. \u201cWe believe it\u2019s going to work and that it\u2019s going to change everything.\u201d\u00a0<\/p>\n

And that\u2019s not because pig organs will replace human-to-human transplants. Those work so well\u2014kidney transplants succeed 98% of the time and often last 10 or 20 years\u2014that pig organs almost certainly won\u2019t be as good. The difference is that if \u201cunlimited organs\u201d really become available, it\u2019s going to vastly increase the number of people who might be eligible, uncorking needs currently masked by strict transplant rules and procedures.\u00a0<\/p>\n

\u201cMany people are not on the list because of the scarcity of organs. Only the most ideal patients get listed\u2014the ones who have the highest likelihood of doing well,\u201d says Montgomery. \u201cThere is a selection procedure that goes on. We don\u2019t really talk about it, but if there were unlimited organs, you could replace dialysis, replace heart assist devices, even replace medicines that don\u2019t work that well. I think there are a million people with heart failure, and how many get a transplant? Only 3,500.\u201d<\/p>\n

A sick child<\/h3>\n

Before becoming a biotech entrepreneur, Rothblatt had started a satellite company; she\u2019d been early to see that with a powerful enough satellite in stationary orbit over the Earth, receivers could shrink to the size of a playing card, an idea that became SiriusXM Radio. But her plans took a turn in the early 1990s, when her young daughter was diagnosed with pulmonary arterial hypertension. That\u2019s a rare disease in which the pressure in the artery between the lungs and the heart is too high. It is fatal within a few years.\u00a0<\/p>\n

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\"Martine
Rothblatt started a biotechnology company, United Therapeutics, after learning that her daughter Jenesis (pictured in background) suffered from a deadly lung disease.<\/figcaption>

AP PHOTO\/JACQUELYN MARTIN<\/p>\n<\/figure><\/div>\n

\u201cWe had a problem: I was going to die,\u201d Jenesis\u2014who now works for United in a project leader role\u2014recalled during a 2017 speech<\/a>.<\/p>\n

Rothblatt and her wife were shocked when doctors said there wasn\u2019t a cure. Rothblatt has compared her feelings then to seeing black or rolling on the floor in helpless pain. But instead of giving up, she began attacking the problem. She would duck out of the ICU where her daughter was and visit the hospital library, reading everything she could about the disease, she has recalled.\u00a0<\/p>\n<\/p><\/div>\n

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Eventually she read about a drug that could lower arterial pressure but had been mothballed by the drug giant Glaxo. She badgered the company until they sold it to her for $25,000 and a promise of a 10% royalty, she recalls. According to Rothblatt, she received in return one bag of the chemical, a patent, and declarations that the drug would never work.<\/p>\n

The drug, treprostinil sodium, did work; it was approved in 2002. You might expect that with just a few thousand patients affected by the disease, it would never make money. Once the drug was available, though, patients started to live, not die, and they needed to keep taking it. A family of related drugs now generates $1.5 billion in sales each year for United.\u00a0<\/p>\n

Though these drugs work well to ease symptoms, patients may eventually need new lungs. Rothblatt understood early on that the drugs were only a life-extending bridge to a lung transplant. Yet there aren\u2019t nearly enough human lungs to help everyone. And that was the real problem.\u00a0<\/p>\n<\/p><\/div>\n

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The most obvious place to get a lot of organs was from animals, but at the time \u201cxenotransplantation\u201d\u2014moving organs between species\u2014didn\u2019t seem to have good prospects. Tests showed that organs from pigs would be viciously destroyed by the human immune system; this \u201chyper-acute\u201d rejection takes just minutes or hours. In the US, some scientists called for a moratorium<\/a> in the face of public panic over whether a pig virus could jump to humans and cause a pandemic.\u00a0<\/p>\n

In 2011 United Therapeutics paid $7.6 million to purchase Revivicor, a struggling biotech company that, under its earlier name PPL Therapeutics, had funded the Scottish scientist Ian Wilmut\u2019s cloning of Dolly the sheep in 1996. Using cloning techniques, Revivicor had already produced pigs lacking one sugar molecule, alpha-gal, whose presence everywhere on pig organs was known to cause organ rejection within minutes. Now Rothblatt convened experts to prioritize a further eight to 12 genes for modification and undertake \u201ca moonshot to edit additional genes until we have an animal that could provide us with tolerable organs.\u201d She gave herself 10 years to do it, keeping in mind that time was running out for patients like Jenesis.\u00a0<\/p>\n

Getting into humans<\/h3>\n

By last year, United had settled on a list of 10 gene modifications. Three of these were \u201cknockouts,\u201d pig genes removed from the genome to eliminate molecules that alarm the human immune system. Another six were added human genes, which would give the organ a kind of stealth coating\u2014helping to cover over differences between the pig and human immune systems that had developed since apes like us and pigs diverged from a common ancestor, 80 to 100 million years ago. A final touch: disabling a receptor that senses growth hormone. Pigs are bigger than we are; this change would keep the organ from growing too large.\u00a0<\/p>\n

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Rothblatt understood early on that the drugs were only a life-extending bridge to a lung transplant.\u00a0<\/strong><\/p>\n<\/blockquote>\n

Organs with these modifications, especially when combined with new types of immune suppression drugs, have been proving successful in monkeys. \u201cI think the genetic modifications they have made to these organs have been incredible. I will tell you that we have primates going for a year with a [pig] kidney with good function,\u201d says Leonardo Riella, director of kidney transplantation at Massachusetts General Hospital, in Boston.<\/p>\n

By 2021, some transplant surgeons were ready to try the organs in humans\u2014and so was Rothblatt. The obstacle was that before green-lighting a formal trial in humans, the FDA, in a meeting that fall, had asked for one further set of monkey experiments that would have all the planned procedures, drugs, and tests locked in and standardized. The FDA also wanted to see consistent evidence that the organs survive for a long time in monkeys\u2014half a year or more,\u00a0 people briefed by the agency say.<\/p>\n<\/p><\/div>\n

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Each experiment cost $750,000, according to Griffith, a transplant surgeon at the University of Maryland, and some doctors felt the monkeys could no longer tell them much more. \u201cWe left that meeting [thinking], \u2018Does that mean we are sentenced for the next two years to keep doing what we were doing?\u2019\u201d Griffith remembers. What they really needed to see was how the organs fared in a human being\u2014a question more monkeys wouldn\u2019t answer. \u201cWe knew we hadn\u2019t learned enough,\u201d he says.<\/p>\n

Montgomery, the NYU surgeon, recalls an hours-long conversation with Rothblatt after which United agreed he could try a kidney in a brain-dead person being kept alive on a ventilator. Because the individual was dead, no FDA approval would be needed. \u201cThe thing about a xenograft is that it\u2019s far more complex than a drug. And that has been its Achilles\u2019 heel. That is why it has remained in animal models,\u201d he says. \u201cSo this was an attempt to do an intermediary step to get it into the target species.\u201d That surgery occurred in September 2021, and the organ was attached to the subject for only 54 hours.\u00a0<\/p>\n

In Maryland, Griffith, a heart surgeon, conceived a different strategy. He asked the FDA to approve a \u201ccompassionate use\u201d study\u2014essentially a Hail Mary attempt to save one life. To his surprise, the agency agreed, and in early 2022 he transplanted a pig heart into the chest of David Bennett Sr.<\/a>, a man with advanced heart failure who wasn\u2019t eligible for a human heart transplant. According to Rothblatt, Bennett was interviewed by four psychologists before undergoing surgery.\u00a0<\/p>\n

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A genetically modified pig heart is prepared for transplantation at New York University in July 2022.<\/figcaption>

JOE CARROTTA\/NYU LANGONE HEALTH<\/p>\n<\/figure><\/div>\n

To observers like Arthur Caplan, a bioethicist at New York University, the use of one-off transplants to gain information raises an ethical question. \u201cSo are you thinking, \u2018This guy is a goner\u2014maybe we can learn something\u2019? But the guy is thinking, \u2018Maybe I can survive and get a bridge to a human heart,\u2019\u201d says Caplan. \u201cI think there is a little bit of a back-door experiment being carried out.\u201d<\/p>\n

Bennett survived two months before his new heart gave out, making him the first person in the world to get a lifesaving transplant from a genetically engineered pig. To Rothblatt, it meant success\u2014even on autopsy, there were no evident signs the organ had been rejected, exactly the result she had been working toward. \u201cThere is no way to know if we could have made a better heart in the allotted time \u2026 [but] this 10-gene heart seemed to work very well,\u201d she told an audience of doctors last April. In Griffith\u2019s view, the organ performed like a \u201crock star.\u201d<\/p>\n

But in the end Bennett died. And in Rothblatt\u2019s lectures, she has elided a serious misstep, one that some doctors suspect is what actually killed the patient. When Bennett was still alive in the hospital, researchers monitoring his blood discovered that the transplanted heart was infected with a pig virus<\/a>. The germ, called cytomegalovirus, is well known to cause transplants to fail. The Maryland team could have further hurt Bennett\u2019s chances as they battled the infection, changing his drugs and giving him plasma.<\/p>\n

Without the virus, would the heart have gone on beating? The closest Rothblatt has come to acknowledging the problem in public was telling a legal committee of the National Academy of Sciences that she didn\u2019t put the blame on the pig heart. \u201cIf I were to put it in layman\u2019s terms, I would say the heart did not fail the patient,\u201d she said.\u00a0<\/p>\n

The bigger problem with the infection, and with Rothblatt\u2019s failure to own the error, is that United\u2019s pigs were supposed to be tested and free of germs. United\u2019s silence is unnerving, because if this virus could slip through, it\u2019s possible other, more harmful germs could as well. Rothblatt did not answer our questions about the virus.<\/p>\n<\/div>\n

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Printing lungs<\/h3>\n

United says that it is now building a new, germ-proof pig facility, which will be ready in 2023 and support a clinical trial starting the following year. It\u2019s not the fantastical commercial pig factory shown in Rothblatt\u2019s architectural rendering, but it is a stepping-\u00adstone toward it. Eventually, Rothblatt believes, a single facility could supply organs for the whole country, delivering them via all-electric air ambulances. Over the summer, she claims, an aeronautics company she invested in, Beta Technologies<\/a>, flew a vertical-lift electric plane from North Carolina to Arkansas, more than 1,000 nautical miles.\u00a0<\/p>\n

Ironically, pigs may never be a source of the lungs that Rothblatt\u2019s daughter may need. That is because lungs are delicate and more susceptible to immune attack. By 2018, the results were becoming clear. Each time the company added a new gene edit to the pigs, hearts and kidneys transplanted into monkeys would last an extra few weeks or months. But the lungs weren\u2019t improving. Time and again, after being transplanted into monkeys, the pig lungs would last two weeks and then suddenly fail.\u00a0<\/p>\n

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\u201cI actually believe there is no part of the body that cannot be 3D-printed.\u201d\u00a0<\/strong><\/p>\n

Martine Rothblatt<\/cite><\/p><\/blockquote>\n

To create lungs, Rothblatt is betting on a different approach, establishing an \u201corgan manufacturing\u201d company that is trying to make lungs with 3D printers<\/a>. That effort is now operating out of a former textile mill in Manchester, New Hampshire, where researchers print detailed models of lungs from biopolymers. The eventual idea is to seed these structures with human cells, including (in one version of the technology) cells grown from the tissue of specific patients. These would be perfect matches, without the risk of immune rejection.\u00a0<\/p>\n

This past spring, Rothblatt unveiled<\/a> a set of printed \u201clungs\u201d that she called \u201cthe most complex 3D-printed object of any sort, anywhere, ever.\u201d According to United, the spongy structure, about the size of a football, includes 4,000 kilometers of capillary channels, detailed spaces mimicking lung sacs, and a total of 44 trillion \u201cvoxels,\u201d or individual printed locations. The printing was performed with a method called digital light processing, which works by aiming a projector into a vat of polymer that solidifies wherever the light beams touch. It takes a while\u2014three weeks\u2014to print a structure this detailed, but the method permits the creation any shape, some no larger than a single cell. Rothblatt compared the precision of the printing process to driving across the US and never deviating more than the width of a human hair from the center line.<\/p>\n

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MICHAEL BYERS<\/p>\n<\/figure><\/div>\n

\u201cI actually believe there is no part of the body that cannot be 3D-printed … including colons and brain tissue,\u201d Rothblatt said while presenting the printed lung scaffolds in June at a meeting in California.\u00a0<\/p>\n

Some scientists say bioprinting remains a research project and question whether the lifeless polymers, no matter how detailed, should be compared to a real organ. \u201cIt\u2019s a long way to go from that to a lung,\u201d says Jennifer Lewis, who works with bioprinting at Harvard University. \u201cI don\u2019t want to rain on the parade, and there has been significant investment, so some smart minds see something there. But from my perspective, that has been pretty hyped. Again, it\u2019s a scaffold. It\u2019s a beautiful shape, but it\u2019s not a lung.\u201d Lewis and other researchers question how feasible it will be to breathe real life into the printed structures. Sticking human cells into a scaffold is no guarantee they will organize into working tissue with the complex functions of a lung. \u00a0<\/p>\n

Rothblatt is aware of the doubters and knows how difficult the technology is. She knows that other people think it won\u2019t ever work. That isn\u2019t stopping her. Instead, she sees it as her next chance to solve problems other people can\u2019t. During an address to surgeons this year, Rothblatt rattled off the list of challenges ahead\u2014including growing the trillions of cells that will be needed. \u201cWhat I do know is that doing so does not violate any laws of physics,\u201d she said, predicting that the first manufactured lungs would be placed in a person\u2019s chest cavity this decade.\u00a0<\/p>\n

She closed her talk with a scene from 2001: A Space Odyssey<\/em>, the one where an ape-man hurls a bone upward and it takes flight as a space station circling the Earth. Except Rothblatt substituted a photograph of herself piloting the zero-carbon electric plane she believes will someday deliver unlimited organs around the country.<\/p>\n<\/p><\/div>\n<\/div>\n

Read More<\/a>
\n Antonio Regalado<\/p>\n","protected":false},"excerpt":{"rendered":"

Organs on demand is one of MIT Technology Review\u2019s 10 Breakthrough Technologies of 2023. Explore the rest of the list here. I met the entrepreneur Martine Rothblatt for the first time at a meeting at West Point in 2015 that was dedicated to exploring how technology might expand the supply of organs for transplant. At<\/p>\n","protected":false},"author":1,"featured_media":596774,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[107978,27830,46],"tags":[],"class_list":{"0":"post-596773","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-dreaming","8":"category-entrepreneur","9":"category-technology"},"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/posts\/596773","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/comments?post=596773"}],"version-history":[{"count":0,"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/posts\/596773\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/media\/596774"}],"wp:attachment":[{"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/media?parent=596773"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/categories?post=596773"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/tags?post=596773"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}