New Hope for Organ Transplantation: Life Without Anti-Rejection Drugs
Rob Waddell dreaded getting a kidney transplant. He suffers from a genetic condition called polycystic kidney disease that causes the uncontrolled growth of cysts that gradually choke off kidney function. The inherited defect has haunted his family for generations, killing his great grandmother, grandmother, and numerous cousins, aunts and uncles.
But he saw how difficult it was for his mother and sister, who also suffer from this condition, to live with the side effects of the drugs they needed to take to prevent organ rejection, which can cause diabetes, high blood pressure and cancer, and even kidney failure because of their toxicity. Many of his relatives followed the same course, says Waddell: "They were all on dialysis, then a transplant and ended up usually dying from cancers caused by the medications."
When the Louisville native and father of four hit 40, his kidneys barely functioned and the only alternative was either a transplant or the slow death of dialysis. But in 2009, when Waddell heard about an experimental procedure that could eliminate the need for taking antirejection drugs, he jumped at the chance to be their first patient. Devised by scientists at the University of Louisville and Northwestern University, the innovative approach entails mixing stem cells from the live kidney donor with that of the recipient to create a hybrid immune system, known as a chimera, that would trick the immune system and prevent it from attacking the implanted kidney.
The procedure itself was done at Northwestern Memorial Hospital in Chicago, using a live kidney donated by a neighbor of Waddell's, who camped out in Chicago during his recovery. Prior to surgery, Waddell underwent a conditioning treatment that consisted of low dose radiation and chemotherapy to weaken his own immune system and make room for the infusion of stem cells.
"The low intensity chemo and radiation conditioning regimen create just enough space for the donor stem cells to gain a foothold in the bone marrow and the donor's immune system takes over," says Dr. Joseph Levanthal, the transplant surgeon who performed the operation and director of kidney and pancreas transplantation at Northwestern University Feinberg School of Medicine. "That way the recipient develops an immune system that doesn't see the donor organ as foreign."
"As a surgeon, I saw what my patients had to go through—taking 25 pills a day, dying at an early age from heart disease, or having a 35% chance of dying every year on dialysis."
A week later, Waddell had the kidney transplant. The following day, he was infused with a complex cellular cocktail that included blood-forming stem cells derived from his donor's bone marrow mixed what are called tolerance inducing facilitator cells (FCs); these cells help the foreign stem cells get established in the recipient's bone marrow.
Over the course of the following year, he was slowly weaned off of antirejection medications—a precaution in case the procedure didn't work—and remarkably, hasn't needed them since. "I felt better than I had in decades because my kidneys [had been] degrading," recalls Waddell, now 54 and a CPA for a global beverage company. And what's even better is that this new approach offers hope for one of his sons who has also inherited the disorder.
Kidney transplants are the most frequent organ transplants in the world and more than 23,000 of these procedures were done in the United States in 2019, according to the United Network for Organ Sharing. Of this, about 7,000 operations are done annually using live organ donors; the remainder use organs from people who are deceased. Right now, this revolutionary new approach—as well as a similar strategy formulated by Stanford University scientists--is in the final phase of clinical trials. Ultimately, this research may pave the way towards realizing the holy grail of organ transplantation: preventing organ rejection by creating a tolerant state in which the recipient's immune system is compatible with the donor, which would eliminate the need for a lifetime of medications.
"As a surgeon, I saw what my patients had to go through—taking 25 pills a day, dying at an early age from heart disease, or having a 35% chance of dying every year on dialysis," says Dr. Suzanne Ildstad, a transplant surgeon and director of the Institute for Cellular Therapeutics at the University of Louisville, whose discovery of facilitator cells were the basis for this therapeutic platform. Ildstad, who has spent more than two decades searching for a better way, says, "This is something I have worked for my entire life."
The Louisville group uses a combination of chemo and radiation to replace the recipient's immune and blood forming cells with that of the donor. In contrast, the Stanford protocol involves harvesting the donor's blood stem cells and T-cells, which are the foot soldiers of the immune system that fight off infections and would normally orchestrate the rejection of the transplanted organ. Their transplant recipients undergo a milder form of "conditioning" that only radiates discrete parts of the body and selectively targets the recipient's T-cells, creating room for both sets of T-cells, a strategy these researchers believe has a better safety profile and less of a chance of rejection.
"We try to achieve immune tolerance by a true chimerism," says Dr. Samuel Strober, a professor of medicine for immunology and rheumatology at Stanford University and a leader of this research team. "The recipients immune system cells are maintained but mixed in the blood with that of the donor."
Studies suggest both approaches work. In a 2018 clinical trial conducted by Talaris Therapeutics, a Louisville-based biotech founded by Ildstad, 26 of 37 (70%) of the live donor kidney transplant recipients no longer need immunosuppressants. Last fall, Talaris began the final phase of clinical tests that will eventually encompass more than 120 such patients.
The Stanford group's cell-based immunotherapy, which is called MDR-101 and is sponsored by the South San Francisco biotech, Medeor Therapeutics, has had similar results in patients who received organs from live donors who were either well matched, such as one from siblings, meaning they were immunologically identical, or partially matched; Talaris uses unrelated donors where there is only a partial match.
In their 2020 clinical trial of 51 patients, 29 were fully matched and 22 were a partial match; 22 of the fully matched recipients didn't need antirejection drugs and ten of the partial matches were able to stop taking some of these medications without rejection. "With our fully matched, roughly 80% have been completely off drugs up to 14 years later," says Strober, "and reducing the number of drugs from three to one [in the partial matches] means you have far fewer side effects. The goal is to get them off of all drugs."
But these protocols are limited to a small number of patients—living donor kidney recipients. As a consequence, both teams are experimenting with ways to broaden their approach so they can use cadaver organs from deceased donors, with human tests planned in the coming year. Here's how that would work: after the other organs are removed from a deceased donor, stem cells are harvested from the donor's vertebrae in the spinal column and then frozen for storage.
"We do the transplant and give the patient a chance to recover and maintain them on drugs," says Ildstad. "Then we do the tolerance conditioning at a later stage."
If this strategy is successful, it would be a genuine game changer, and open the door to using these protocols for transplanting other cadaver organs, including the heart, lungs and liver. While the overall procedure is complex and costly, in the long run it's less expensive than repeated transplant surgeries, the cost of medications and hospitalizations for complications caused by the drugs, or thrice weekly dialysis treatments, says Ildstad.
And she adds, you can't put a price tag on the vast improvement in quality of life.
NASA Has the Technology to Save Us From an Asteroid Strike, But Congress Won’t Fund It
At the biannual Planetary Defense Conference earlier this year, NASA ran a simulation of an asteroid slamming into the center of Manhattan.
For several millennia now, we've been lucky, but our luck won't hold out forever.
The gathering of astronomers, planetary scientists, and FEMA disaster-response experts attempted a number of interventions that might be possible within a time window of eight years, the given warning period before impact.
Catastrophic asteroid crashes are not without precedent, and scientists say it's only a matter of time before another one occurs—that is, if we do nothing to prevent it. It's believed that a huge asteroid crash off the coast of Mexico's Yucatan Peninsula created a worldwide disaster that helped to speed the extinction of the dinosaurs 65 million years ago.
In 1908, a meteoroid less than 300 feet in diameter exploded in the air over the Tunguska region of Siberia, creating a shockwave that leveled trees for hundreds of square miles. It's a matter of sheer luck it didn't hit a major population center, where human casualties could have been enormous.
For several millennia now, we've been lucky, but our luck won't hold out forever. There are millions of asteroids circulating about in our solar system, some of them hundreds of miles across, and although the odds of a massive one crashing to Earth in the near future is statistically low, the devastation could be apocalyptic.
Back at the conference, the experts tried sending several spacecrafts to knock the asteroid off-course by slamming into it. They considered blasting it with nuclear weapons. They even considered painting it white so it absorbed less of the sun's energy, hoping that would shift the asteroid's trajectory. In the simulations, all of the interventions failed and the giant space rock crashed into Manhattan, killing 1.3 million people in a massive explosion that was 1,000 times more powerful than the Hiroshima bomb.
NEOCam is designed, tested, and ready to build, but the project is currently frozen because of a $40 million gap in NASA funding.
Given more time, the scientists said, they might have succeeded in preventing the disaster. However, with today's asteroid-hunting telescopes, it's not likely we would have more warning. Our current telescopes are not powerful enough to detect all the near-earth asteroids, nor are they positioned well enough for sufficient detection. As recently as last week, for example, an asteroid traveling 15 miles a second narrowly missed crashing into the Earth, and it was only noticed several days in advance.
Now for the good news: There is a new technology that could buy us the time we need, says MIT planetary sciences professor Richard P. Binzel and colleagues who attended the conference. The Near-Earth Object Camera, or NEOCam, designed by NASA's Jet Propulsion Laboratory, would detect more than 90 percent of nearby objects that are 420 feet across or larger, according to Binzel.
The powerful infrared telescope is designed to sit within the L1 Lagrange point, a stable location in space where the gravitational pulls of the Earth and the sun cancel each other out. From there, large space bodies could be detected early enough to give scientists decades of warning when an asteroid is heading for Earth. NEOCam is designed, tested, and ready to build, but the project is currently frozen because of a $40 million gap in NASA funding.
The status of NEOCam, according to Binzel, is a case-study in short-sightedness and a lack of leadership. Congress needs to raise NASA's Planetary Defense budget from its current $160 million to $200 million to get the telescope built and launched into space, a goal that would seem eminently doable within the strictures of 2020's $4.75 trillion government budget. But Binzel describes a current deadlock between NASA, Congress, and the Office of Management and Budget as a "cosmic game of chicken."
If we don't use our technology to defend the planet, "it would be the most epic failure in the history of science."
In an excruciatingly budget-conscious atmosphere, "No one wants to stick their neck out and take adult responsibility" for getting the funding allocated that would unfreeze the project, says Binzel. But, he adds, "We have a moral obligation to act."
NEOCam would not only spot the overwhelming majority of asteroids in Earth's vicinity, it would determine their size and pinpoint exactly where they are likely to strike the Earth. And it would allow us decades to act, according to Binzel. Repeated ramming by an international armada of specialized spacecraft could slightly change the trajectory of an asteroid, he says. Changing the trajectory only a tiny bit, given the scale of millions of miles and several decades for the course change to take effect, could cause an asteroid to miss the Earth altogether.
"So far we've been relying on luck," says Binzel, "but luck is not a plan." Now that we have the technology to discover what's careening through our space neighborhood, it's our ethical duty to deploy it. If we don't use our technology to gain the knowledge we need to defend the planet, Binzel concludes, "it would be the most epic failure in the history of science."
Should Congress green light the $40 million budget for the new asteroid-hunting telescope? @NASA #NASA #astroid— leapsmag (@leapsmag) 1564681293.0
A ‘Press Release from the Future’ Announces Service for Parents to Genetically Engineer Their Kids
Most people don't recognize how significantly and soon the genetic revolution will transform healthcare, the way we make babies, and the nature of the babies we make. The press release below is a thought experiment today. Within a decade, it won't be. * * *
Genomix Launches uDarwin, a New Business to Help Parents Optimize the Health, Well-Being, and Beneficial Traits of their Future Offspring
NEW YORK, July 29, 2029 /PRMediawire/ -- Genomix, a Caribbean-based health and wellness company, today announced the launch of uDarwin, a discrete, confidential service helping parents select and edit the pre-implanted embryos of their future children.
"Our mission is to help prospective parents realize their dream of parenthood in the safest manner possible while helping them optimize their future children's potential."
"We often fetishize nature," said Genomix Medical Director and Co-Founder Dr. Noam Heller, "but the traditional process of conception through sex confers risks on future children that can be significantly reduced through the careful and safe application of powerful new technologies."
Approximately three percent of all children are born with some type of harmful genetic mutation. Through its patented process of extracting eggs from the prospective mother, fertilizing these eggs with sperm from the intended father or from one of the superstar donor samples in the proprietary uDarwin gene bank, and screening up to twenty of these embryos prior to implantation, this risk can be brought down to under one percent.
"Having a baby is the most intimate and important experience in most people's lives," said Genomix CEO and co-founder Rich Azadian. "Our mission is to help prospective parents realize their dream of parenthood in the safest manner possible while helping them optimize their future children's potential."
In addition to screening pre-implanted embryos to significantly reduce disease risk, uDarwin uses its proprietary algorithm for the "polygenic scoring" of embryos to directionally predict potential future attributes including healthspan, height, IQ, personality style, and other complex genetic traits. Attributes once accepted as being the result of fate or chance can now increasingly be selected by parents from among their own natural embryos using this entirely safe process.
A premium product offering, uDarwin+, provides parents the opportunity to make up to three single gene mutations to their selected embryo to reduce a risk or confer a particular benefit. Among the most popular options for this service include increased resistance to HIV and other viruses, a greater ability to build muscle mass, and enhanced cognition. Additional edits will be made available as the science of human genome editing further advances.
Jamie Metzl's new book, Hacking Darwin: Genetic Engineering and the Future of Humanity, explores how the genetic revolution is transforming our healthcare, the way we make babies, and the nature of and babies we make, what this means for each of us, and what we must all do now to prepare for what's coming.
"uDarwin is proud to be the first company in the world offering the highest level of reproductive choice to parents," Mr. Azadian continued. "Genetic technologies are allowing us for the first time to crack the code of our health and identity. As pioneers in applying the most advanced genetic technologies to human reproduction, we recognize that prospective parents' desire for the services we offer exceeds societal levels of comfort with this technology. Our highest levels of customer service, comfort, and confidentiality ensure parents can secure massive benefits for their future children while avoiding unnecessary attention or any compromise of privacy."
All uDarwin services will be carried out in the company's state-of-the-art clinic aboard a super-luxury 500-foot yacht operating in international waters. After applying on the secure uDarwin website and gaining approval, clients are provided a date, time, and location to meet a company representative at a conveniently located Caribbean marina from where they will be shuttled to the uDarwin clinic. "Pioneers have always traveled beyond boundaries to create new possibilities," Mr. Azadian added. "Conceiving a child in a location where it can receive the greatest benefits of advanced science is no different."
"Pioneers have always traveled beyond boundaries to create new possibilities."
The cost of the basic uDawin service is $5 million, with half paid up front and half paid following the successful birth of a baby. Charges for uDarwin+, premium sperm or egg donors, surrogates, and other services are additional. "uDarwin is not for everyone," Mr. Azadian said, "but most parents of significant means understand that the benefits of optimal genetics far exceed almost any monetary cost."
"The genetic revolution has already begun," Medical Director Heller added. "The question for prospective parents is whether they want to be the last parents who left the health and identity of their future children to chance or the first to give their future children the greatest chance of optimal health and maximal fulfillment in the new reality that will arrive far sooner than most people appreciate."
If you could genetically alter your future children, would you? https://t.co/N0tqwX4Qd3— leapsmag (@leapsmag) 1564426548.0