With chest hair and hospital scrubs sneaking out from beneath his white lab coat, Dr. Shaf Keshavjee seems armed for the future of lung transplantation. The director of the Toronto Lung Transplant Program and surgeon-in-chief of the University Health Network sees promise in advances that can keep lungs working outside the body longer than ever. What it means, he hopes, is that one day surgeries can be prescheduled instead of surprising staff at, say, 3 a.m. He also praises industry peers who are generating new lungs in labs. “In the future,” he speculates, “can we take organs off the shelf out of the cupboard and just say, ‘OK, I need a size 8 lung,’ and put it in?”
Keshavjee’s vision might seem more grounded in fiction than science, though this guy helped create the world’s first organ repair center, in Toronto, nine years ago. That process centralized and streamlined lung transplants while boosting the number of procedures by around 50 percent annually, to 150, and it’s now being used in a facility in Maryland, with similar buildings planned for Florida and Arizona. Next up for the doc: getting the prototype for a new device to market this spring that will assess and repair otherwise unusable donor lungs. Keshavjee wants “super” lungs.
Can we make a lung that will outlive the recipient?
Dr. Shaf Keshavjee, director, Toronto Lung Transplant Program
New scientific breakthroughs could dramatically change the landscape for patients gasping for a fresh set of lungs. Some work involves repairing damaged donor organs, while other research is moving us closer to genetically engineered animal organs that could be placed in humans without getting attacked and destroyed by viruses. And certain techniques are prolonging how long transplant recipients can survive without their own lungs physically inside their bodies — to a record six days, in one recent case. Advances like these have the potential to improve all sorts of important metrics: medical costs, surgery times, hospital errors and, arguably the biggest factor of all, patient longevity. “The goal, I say in our lab, is can we make a lung that will outlive the recipient?” says Keshavjee. “A person who has lung disease should never face lung failure again.”
Scientists aren’t there, yet. These days, if you breathed air into a new set of lungs for a month, the odds of survival would hover near 97 percent. But by year three, that would deflate to a little more than 68 percent. Of course, there’s no guarantee you’d even get a lung. In the U.S., more than 1,300 people sit on a waiting list, according to a transplant tracker from the Department of Health and Human Services. Part of the solution is to encourage more people to give up their lungs if they die. But by the time these organs are harvested, packed and delivered, around 80 percent of them are too damaged to transplant or are otherwise unusable.
Gordana Vunjak-Novakovic listened to these kinds of challenges when a lung transplant surgeon reached out for help several years ago. Inspired, Vunjak-Novakovic — the director of Columbia University’s laboratory for stem cells and tissue engineering — has since co-led a multidisciplinary team of researchers in developing a procedure that repairs the damage many lungs incur during trips to recipients. The approach, published this year in Nature Biomedical Engineering, includes storing an organ in a chamber for days while ventilating it with air and perfusing it with the recipient’s blood and stem cells. This helps maintain a fully functional lung outside of the body for up to 56 hours — the longest known time for a lung recovered from injury, says Vunjak-Novakovic. The procedure might have worked even longer, but the study, which relied on pigs, was designed and permitted to run only that long. Now, Vunjak-Novakovic’s team will turn to trials with human lungs. “There is still a lot to do until we come to clinical use,” she says.
There’s a similar caveat for other procedures that recently have generated glee in the industry. This summer, a life sciences company called eGenesis, which was co-founded by Harvard geneticist George Church, shared how it used the gene-editing tool CRISPR in pigs to deactivate viruses that could infect people who receive a new organ from an animal. It’s still too early to say whether the procedure could enhance pig organs to work as well as swimmer Michael Phelps’ lungs, though when Church was asked about this very point, he reportedly said the organs will go through safety and efficacy testing, including “making sure they’re robust, and maybe they have to be as robust as Michael Phelps’ in order to do the job.” (The company didn’t respond to OZY’s request for comment.)
A lot has changed since June 11, 1963, when James Hardy performed the world’s first human lung transplant on a convicted murderer in Mississippi. The patient survived just 18 days. Subsequent recipients survived only days, or weeks, until 1983 — when the first human double-lung transplant recipient, known as patient No. 45, left a Toronto hospital and lived more than six additional years.
In January, Toronto once again drew international acclaim after it was revealed that Keshavjee, along with two additional thoracic surgeons and 10 operating room staff, pulled off a world’s first. They had removed the severely infected lungs of Melissa Benoit, a mom from Ontario who was expected to die within hours, and kept her alive without them for six days using advanced life-support technology, including an artificial lung, heart and kidney. The time helped her recover, but also, Keshavjee notes, “We didn’t have new lungs in her case yet.” The operation was heralded as a great success, though what hasn’t been reported since, outside of a brief obituary notice, is that Benoit recently passed away. The cause: an ear infection that ultimately led to septic shock. “We were totally devastated,” Keshavjee says.
