The decade ahead will be known for many dramatic health advances, but few will be more astonishing or impactful than the miracle of organ regeneration. In just a matter of a few years, people in dire need of a healthy heart, liver, kidney, or set of lungs will not need to wait for a donation.
Martine Rothblatt, Ph.D., is one of the many brilliant scientists breaking through this vast frontier. Her company, United Therapeutics, is changing the game with a multitude of options for life and death organ transplants, and paving the way for an unlimited supply of transplantable organs to be available on-demand.
EVLP: Restoring Lungs That Would Otherwise Be Discarded
End-stage lung disease steals a quarter of a million lives each year, and sadly, one of the primary reasons is because the chances of a person who needs a lung actually receiving one are very low — just one percent of people in 2019.
The reason is that lungs are fragile and very complex — so when a registered donor dies, the vast majority of them are ruled out by disease. Among the few lungs that make the cut, 80 percent become filled with mucus and other fluids and are discarded.
One of many approaches to organ regeneration that Martine has massively scaled is Ex Vivo Lung Perfusion (EVLP), a technique in which “dead” lungs that would otherwise be thrown out are restored and preserved for up to 22 hours — enough time for them to be flown out for transplantation.
Building on the work of Dr. Shaf Keshavjee, a surgeon at Toronto General Hospital, Martine established the world’s first centralized lung restoration facility in Silver Spring, MD, where she and her team take “dead” organs that have been rejected for transplantation and revive them with special solutions under a glass dome that acts as an artificial body.
Once stabilized, a bronchoscope sends a real-time video to surgeons around the U.S.— and if it meets their standards, it is cold-packed and flown out for transplantation. In every single case that a surgeon has remotely accepted a lung, according to Martine, the patients have walked out of the hospital.
The Humanization of Pig Organs using CRISPR Technology
While EVLP lungs are an incredible advancement, one of the issues with the technique is that the organs don’t always get to patients in time, and the process relies on other people dying sudden and untimely deaths. In an ideal world, Martine imagined having a pipeline of off-the-shelf organs, ready at an hour's notice. But where would the organs come from?
One solution she found is in the pig, whose heart valves are already being used in human patients — but unfortunately, not without some serious complications. Within hours of a xenotransplant from a pig, an extremely destructive immune response is often provoked. Looking at this problem as a thrilling opportunity, Martine teamed up with Craig Venter, the “master of genomic sequencing,” to humanize the pig — in other words, delete the pig proteins that trigger the rejection in humans.
Using CRISPR, a relatively new but proven technology that can essentially cut, paste, copy and move genes around, Martine and Venter discovered that a “ten-gene pig”— an animal with a mere ten problem genes knocked out or replaced by human DNA — could be transplanted into a human without triggering an immediate rejection.
The technology is proving to be successful. In January 2022, a pig kidney was transplanted into a human without triggering an immediate rejection for the very first time, and even looked like a normal kidney the following day.
In another groundbreaking feat, a group of surgeons from the University of Alabama at Birmingham have successfully transplanted kidneys from a genetically altered pig into the abdomen of a brain-dead man. According to the surgical team, the kidneys functioned normally, making urine after about 23 minutes and doing so for three days. The surgeons reported to the New York Times that they hope to start clinical trials with kidney patients in late 2022.Martine is aiming to kick off her own clinical trials for xenokidneys by 2023, and for xenohearts by 2025, and is confident that pig organ transplants for human patients will be an FDA-approved reality before the 2030s.
The Final Frontier for Bioprinting: Hearts, Kidneys, Livers, and Lungs
While stem cells have been used to 3D print skin, bladders, ears, and eyes for years, manufacturing complex organs, like hearts, kidneys, livers, and lungs is a much more difficult challenge to overcome, and the timeframe for this achievement is estimated in decades. As usual, Martine is in a hurry — and has partnered with the world’s leading 3D-printing company, 3D Systems, to gun for FDA approval by 2028.
The technology is still a work in progress, and Martine has no doubt they’ll get there. Once the “how” problems are solved, a ready-made lung or heart can be grown in less than a month. The beauty of bioprinted organs is that they can be created on-demand, and tailored for people of all ages, sizes, and shapes — all over the world.
