Organ shortages cause preventable deaths, risky transplants, and tough decisions about who to prioritize.
Scientists have made progress this year on experimental paths to make more organs available.
From gene-edited pig hearts to growing synthetic embryos, here's what researchers are trying.
Leilani Graham's heart stopped suddenly for the first time when she was 13. She suffered three more cardiac arrests until, at 24, she had to have her heart replaced.
She was lucky to have gotten a heart. On average, 17 people die every day on the waiting list, out of nearly 106,000 people listed for a transplant. Some never even make the waiting list.
But Graham would have picked a different heart if she'd had a choice. Coming from a 52-year-old donor, it was a risky, or "marginal," donation - one of many Band-Aid fixes for the lack of organs across the US.
When the time comes to replace her heart again - sooner rather than later, she fears, because of its age - she'll likely be lower on the list than people awaiting their first transplant.
Between deadly delays, marginal donations, and sticky ethical questions about who gets prioritized for transplants, the shortage of life-saving organs is a medical crisis. That's why researchers are pursuing everything from pig organs to blood-type conversions in order to make more hearts, lungs, and kidneys available.
"The idea of getting an organ that didn't necessarily have to come from a dead donor, that could come from a pig that has been genetically modified, is something that definitely intrigues me," Graham told Insider. She now sits on an ethics advisory committee for transplant research at New York University Langone Hospital, including pig-organ research.
If pig organs turn out to be just as effective as human organs, she added, "That is more appealing to me than using marginal donors."
While much of the shortage is driven by imperfect logistics and bureaucracy rather than supply, cutting-edge research could make organs - human, pig, or synthetic - more accessible in Graham's lifetime.
Here's what researchers are trying.
Transplanting organs from genetically engineered pigs to humans
In January, surgeons at the University of Maryland Medical Center transplanted a pig heart into a human patient for the first time. Hospitals had declined to list the man, David Bennett, for a human heart because supplies are short and he had a history of failing to follow doctor's orders. The pig-heart procedure was highly experimental.
"It's got danger written all over it," Arthur Caplan, a bioethics professor at NYU, told Insider at the time, saying it would be a "miracle" if the man survived. Two months later, Bennett died, possibly related to a pig virus lurking inside his new heart.
NYU Langone is taking a more incremental approach to learning to put pig organs into human bodies.
This year, researchers there transplanted genetically modified pig kidneys into two deceased humans, then pig hearts into two brain-dead humans. Eventually, if procedures like this continue to be successful, they could move into phase 1 clinical trials with consenting patients like Bennett.
"There will be an iterative process of learning, changing tactics," Dr. Robert Montgomery, director of NYU Langone Transplant Institute, said during a press conference in July.
He added that he hopes gene-edited pigs will become a "renewable, sustainable source of organs, so no one will have to die waiting."
Stopping organ decay after death
In a study published in August, researchers at Yale School of Medicine restored dead pigs' heartbeats and stopped organ decay, seemingly halting the death of cells. If the technique works for human organs in the future, it could allow clinicians to preserve many more organs for donation after death.
One hour after the pigs died, the researchers connected them to a system of pumps, heaters, and fillers called OrganEx. By artificially flushing the pigs' organs with blood - a process called perfusion - they restored molecular and cellular function in the heart, brain, liver, and kidneys.
The hearts even contracted to pump blood, indicating renewed electrical activity, and restored full blood circulation in the pigs' bodies. There was no sign of electrical activity in the brain. Still, the scientists say they've uncovered a previously unknown capacity for mammal cells to recover after blood has stopped flowing.
"Cells actually don't die as quickly as we assumed that they do, which basically opens up the possibility for intervention," Zvonimir Vrselja, a neuroscientist on the research team at Yale, said in a briefing at the time. "If properly intervened, we can maybe tell them not to die."
Changing organs' blood type
Part of the reason getting an organ can be difficult is because it has to be compatible with the patient's blood type. Some researchers are working to eliminate that criterion.
In a February paper, scientists announced they had removed the Type A antigens, or signature sugar molecules, from the blood of human lungs. If a person receives an unmatched organ, the organ's antigens activate the body's immune response, which can lead to rejection. Type O blood and organs don't have antigens and can be donated to anybody of any blood type. So the researchers essentially converted Type A lungs into universal lungs.
The conversion may have been temporary, but they plan to run more trials in mice.
At Northwestern University Medical Center, surgeons recently took the opposite approach: scrubbing antigens from the blood of the transplant patient. Using this method for the first time, they transplanted mismatched lungs and kidneys into a living patient and sent her home in August, The Chicago Tribune reported.
Growing synthetic organs from stem cells
Some scientists believe they could one day grow synthetic organs using stem cells - self-replicating, nonspecialized cells, which develop into all the other types of cells in our bodies.
In an August paper, researchers announced they had grown synthetic embryos from mouse stem cells, with no eggs, sperm, or womb.
"The embryo is the best organ-making machine and the best 3D bioprinter - we tried to emulate what it does," Jacob Hanna of Weizmann's Molecular Genetics Department, who headed that research team, said in a statement.
Hanna started a company called Renewal Bio to pursue the possibility of turning stem cells into organs for transplants. But much more research is needed before growing human embryos this way.
Tricking the body into accepting a new organ without immune-suppressing drugs
In June, a team of Stanford physicians announced that they had transplanted new kidneys into three children who had a rare genetic disease, and the children didn't need immune-suppressing drugs afterward.
Normally, transplant patients take medication for the rest of their lives so that their bodies don't launch an attack against their new organ. That doesn't always prevent rejection and it significantly increases risk of cancer and various infections. Eliminating the need for immune-suppressing drugs could increase the quality and length of transplant patients' lives.
"Everybody I know who's a transplant patient has shielded from COVID and had to really change their lifestyle for the past couple years. So getting rid of immunosuppression would be incredible," Graham said.
The Stanford doctors first injected the children with stem cells from the bone marrow of their parents, who were also their organ donors. They hoped that those stem cells would mature into immune cells, arming the children with new immune systems that would recognize their new organs. Five to 10 months later, they transplanted the kidneys. At the time of the report, two or three years after the procedures, the children were back in school, playing sports, with no signs of illness and no immunosuppressants, the doctors reported.
"I just think it's important to highlight the good work that doctors are doing to try to increase quality of life, and then the bravery of the patients who are willing to undergo it," Graham said.
Hilary Brueck and Marianne Guenot contributed reporting.