Starzl’s Growing Shadow

Brothers Tim and Joe Scherer have always been close. They play on the same men’s softball team in Beaver County. They talk on the phone every day. Whenever one needs help on their home, they’re there for each other. In August 2015, Tim learned he needed a kidney. For reasons unknown, his body attacked his kidneys. He woke up one day, hardly able to breathe; fluid filled his lungs because his kidneys couldn’t filter toxins out of his body. He was 32. His youngest brother, Joe, was a new dad in his 20s. Joe never hesitated to offer his own kidney.

“I immediately started Googling about donating an organ,” Joe recalls. “Tim didn’t even have to ask. I just thought, ‘You tell me where to sign and I’ll do it.’”

Not only did Tim’s brother step up but so did many others. His father, his wife’s best friend, co-workers, his father-in-law, even his octogenarian grandfather. “It blows my mind,” Tim says, that he never had to ask any of them. “It’s hard enough to ask people for favors. How do you ask for an organ?”

In September, Tim and Joe both went into surgery at Allegheny General Hospital, part of Allegheny Health Network. Dr. Lorenzo Machado removed Joe’s organ. Another surgeon, Dr. Tadahiro Uemura, put it into Tim.

Once considered impossible and miraculous, transplantation is standard therapy now for an array of diseases that attack the heart, lungs, liver, pancreas and, most commonly, the kidneys. It’s far superior, for example, to dialysis as a treatment for end-stage kidney failure.

Father of transplantation

Much of the credit for the success of transplantation goes to the pioneering work of the University of Pittsburgh’s Dr. Thomas E. Starzl. He passed away at 90 earlier this year. For more than half a century, Starzl devoted his life’s work to advancing transplantation. He helped perfect the medications needed to keep the immune system from attacking what it saw as a foreign invader. Attempting to overcome a chronic shortage of organs, Starzl was the first to perform cross-species organ transplants.

“The world has lost the greatest figure in the history of transplant, and I have lost my greatest mentor,” says Dr. Abhinav Humar, clinical director of the Thomas E. Starzl Transplantation Institute and chief of the Division of Transplantation at UPMC. He adds, “The Starzl Transplant Institute will continue to work tirelessly to carry on his rich legacy. While we’ve made tremendous progress, there are still a lot of problems in transplant that need ongoing vigilance.”

One of Starzl’s unrelenting goals was to see transplant recipients achieve tolerance—where the immune system would accept the foreign organ. With few exceptions, the vast majority of transplant recipients today need to take a lifelong cocktail of drugs to suppress their immune system, often causing other complications such as infections. Years ago, Starzl had a theory, if you let a person’s immune system first try to fight off the foreign organ, its innate turn-off switch would eventually activate.

“This has been a very appealing idea,” says Dr. Fadi Lakkis, who was handpicked by Starzl a decade ago to serve as scientific director of Pitt’s Transplantation Institute. “The problem is,” Lakkis adds, “how do you let the immune system run its course without destroying the organ? It’s been attempted, but it’s been difficult to achieve with all types of organs.”

UPMC is about to take a major step toward achieving the holy grail of tolerance. Researchers hope to soon launch the first attempt to inject a certain type of donor immune system cells into the recipient of a liver from a living donor. “The idea—based on the pioneering work of Angus Thomson, distinguished professor of surgery at Pitt—is to take monocyte cells from the donor, modify them in a lab, then inject them into the recipient one week prior to transplant,” Lakkis says.

A phase 1 trial to test the safety of this procedure has been FDA approved and is expected to start this summer and enroll about a dozen people. Results from a similar trial involving monkeys showed the procedure to be safe and effective in achieving immunosuppression withdrawal in some animals.

“The liver was chosen because of the strength of our program to do living liver transplantations. Also, the liver is the organ least likely to be rejected,” Lakkis says.

A similar trial in the pipeline will involve kidney recipients. “In a way, these trials are inspired by Dr. Starzl’s idea that you have to provoke the immune system before you shut it down,” Lakkis says. If these trials work, he adds, “It won’t get all transplant recipients off immunosuppressant medicine but it would be a very significant advancement.”

Because experts have largely perfected the art of keeping the immune system in check, organ transplants can last years and even decades. “We’ve come a long way with medication. You need to keep drug levels in a tight window because the same drug that saves your transplant can also damage your transplant if you run levels too high,” says nurse Janice Glidewell, who has worked with transplant patients since 1992 and now directs the transplant program at Allegheny General Hospital.

Low levels of anti-rejection drugs can have devastating consequences, too. One week last summer, Erik Cook, 36, of Beaver Falls didn’t have access to the medications he takes morning, noon and night when his health insurance was being switched to a new plan. (Cook has a kidney from his wife and a pancreas from a deceased 23-year-old man after his own organs were damaged by type 1 diabetes he developed as a child). The week he didn’t have coverage for his medicines, his body immediately started to attack the pancreas he had received in May 2015 at UPMC. It was a close call, but his UPMC doctors were able to halt the rejection process. “It was very scary. It’s been a really long ordeal. But his pancreas has come back and it’s working again,” says his wife, Michaela Cook.

Can pigs solve the shortage?

In the 1960s, Dr. Starzl performed the first baboon-to-human organ transplant. Always pushing the envelope, his motivation to perform cross-species (xenotransplants) came from the fact that there are never enough donor organs available. Today in the U.S., 22 people die each day waiting for an organ. While animal-to-human transplants never gained traction during Starzl’s career, it is re-emerging, thanks to advances in genetic engineering. “Our group worked closely with the company that genetically modified the pig to make its organs more acceptable to humans,” Lakkis says.

“Surgeons take tendons, heart valves and other parts from a pig now, but that’s a little different. It doesn’t require the same degree of viability as a whole organ,” Lakkis says. “There is concern that pigs would harbor viruses that could get activated in humans. There’s no evidence of that but it is a theoretical concern.” There would be ethical issues to address as well.

Until cross-species transplantation becomes a viable option, living donations are a godsend for those who need a new kidney or a liver. The kidney is always the organ most in demand. About 80,000 Americans are waiting for one today. This need will likely continue to grow. “Right now, two of the most common causes for kidney failure are not the genetic diseases from the past. They are diabetes and high blood pressure,” Lakkis says. “Those two diseases exist as a syndrome, metabolic syndrome, and go along with obesity and hyperlipidemia. Usually these patients will have one, two or all four of these conditions that are synergistic.”

Living kidney and liver donations are possible because humans have two kidneys but can do fine with only one. The human liver also comes with a lot of redundancies and has the unusual ability to grow back to its normal size after a section is removed.

Today, about half of all kidney transplants come from living donors. But among liver transplants, only a small portion—3 to 4 percent— come from living donors. Living liver transplants are highly complex so few centers offer them. UPMC is a leader in this field: “About 30 to 40 percent of transplants we’re doing for the liver are with living donations,” Humar says.

The real miracle of transplantation today, adds AGH’s Machado is “For someone to give that gift of life to a loved one and specifically to someone they don’t even know. To me, that is amazing.” He adds, “We talk about sports heroes all the time but truly these are the people we should be looking up to. They are doing a selfless act to impact someone else’s life.”

Brotherly bond

Without his brother’s gift, Tim Scherer would have likely waited 3 to 5 years for a cadaver kidney to become available. He was among about 30 living kidney transplants done in 2016 at AGH. (AGH does twice as many cadaver kidney transplants and has the region’s highest survival rates for heart transplants).

Allegheny General Hospital ranks as the top heart transplant program in the Pittsburgh area—and second in the state behind the Hospital of the University of Pennsylvania.

The kidney Tim got from Joe started to work immediately. Joe admits the first week after his surgery was tough. “I remember lying in bed and with any sort of movement, I could feel either my other organs moving or air moving around.” For a while, he couldn’t pick up his older child, but he could hold his infant daughter. “I have no regrets,” Joe says. “My brother looks completely normal. I don’t feel any different. If I didn’t have my scar, I wouldn’t be able to tell that I gave away a kidney.” Joe knows if the situation had been reversed, his brother would have done the same.