Like most 17 year olds, Owen Jennings is aware of how he looks. So, when he glances in the mirror before bed and notices that the whites of his eyes are a bit yellow, he's momentarily startled. But he figures that after he gets a good night's sleep, his eyes will be fine.
When he awakens the next morning, his eyes aren't fine. Neither is the rest of his body, which has turned yellow, too. His mom rushes him to the local hospital in northern New Jersey. Tests show he's in acute liver failure, and he's immediately transported to New York Presbyterian/Columbia University Medical Center in Manhattan.
He can't remember much else during the next few days. If he could, he'd recall being kept alive by tremendous amounts of steroids, paired with blood and plasma transfusions, and immediately being placed on the liver transplant list. Family members begin the process of being screened to see whether anyone is an ideal match.
Then, suddenly, his body rebounds. Tests show that his liver enzyme counts have plateaued; soon they fall back within a normal range. Subsequently, he's taken off the transplant list. Given the harrowing process that is organ transplantation, it makes more medical sense to see how far he can get on medication alone. He remains on heavy doses of steroids, and soon a drug called Imuran is added, an anti-organ-rejection medication that convinces his body to leave his liver alone but at the cost of also weakening his immune system, which raises his risk for cancer and overall illness.
Feeling better, he begins to process his diagnosis: type II autoimmune hepatitis, a rare genetic condition. He must make peace with the reality that for the rest of his life he will need to monitor his liver counts every month as well as take a daily regimen of medication that has harmful side effects. He wonders whether organ transplantation will be safer when his time comes. He hopes that someday "successful" transplants last longer than 10 years before yet another replacement must be sought. He hopes we come to understand the human immune system so we can harness its healing power for conditions such as his. He hopes that when his liver has endured as much stress as it can take—and that time will come, according to his doctors—a liver transplant won't be such a traumatic ordeal.
Jennings, now 26, lives in San Francisco today and works in technology within the financial field. Preferring to focus on an optimistic future, he happily reports that he has met his "soulmate," whom he plans to marry, and he doesn't let himself obsess over the latest advancements, or setbacks, of organ transplantation.
Someone else does, though. Yoed Rabin has dedicated much of his professional life to one day helping patients around the world who are struggling with compromised organs and tissue.
Rabin, a professor of mechanical engineering at Carnegie Mellon University, heads the Biothermal Technology Laboratory. His lab is located in Hamerschlag Hall, named for the school's first president, in one of the original yellow brick buildings constructed when the school was still known as the all-male Carnegie Institute of Technology. The Pittsburgh-based coed university is known for innovation—it's home to the world's first robotics graduate program, offers the country's only bagpipe major, and is the birthplace of cognitive psychology.
Yoed Rabin works to harness the healing powers of extreme cold—those that preserve, as well as destroy, in the name of health.
Rabin's lab features the seeming disorganization of young researchers—desks strewn with coffee mugs and notes alongside computers loaded with complex data that reaffirm their brilliance. There are two dorm-style refrigerators—one marked for food, the other warning against it—as well as a scanning cryomacroscope, a proprietary device Rabin invented that allows one to monitor how well, or poorly, large tissue samples sustain extreme cooling and rewarming. There are also vats of liquid nitrogen, an essential component in his work. They somewhat resemble R2-D2.
Here is where Rabin is researching and perfecting cryopreservation, which entails preserving organs and tissues below freezing so they're indefinitely ready for transplants—on-demand, off-the-shelf. The impact of this technology could be limitless: Organ banking stands to save more lives than even a cure for cancer, as more people in the United States die from organ impairment than cancer or heart disease each year, according to the Centers for Disease Control and Prevention.
If organs can be banked via cryopreservation, then someone like Jennings would know that a liver from a deceased donor (who had been around his weight, with his blood type) would be available the moment Jennings needed it. It would also give him time to take immunosuppressing drugs or perhaps follow immune tolerance induction protocols (100% free of drugs) to prep his body for the transplant, vastly increasing the odds his body would accept the organ.
Cryopreservation has been a natural progression from Rabin's earliest biothermal research—cryosurgery. In its most advanced form, this is a minimally invasive surgical procedure that relies on liquid nitrogen–cooled probes and medical imaging to freeze hostile tissue, such as cancerous tumors, and destroy them.
In essence, Rabin works to harness the healing powers of extreme cold—those that preserve, as well as destroy, in the name of health.
As a world expert on thermomechanics and biothermal technology, he's often called on to speak at conferences around the globe and is a go-to source for such heavy hitters as the Department of Defense and the Organ Preservation Alliance, which is a non-profit that is incubated at SU Labs at NASA's Research Park in Silicon Valley. He has been a pioneer in the field of cryobiology, which isn't to be mistaken with cryonics. Cryonics is a process where people freeze their bodies, or in some cases just their brains, in the hopes that one day they might be brought back to life in a future where technology has improved to cure ailments incurable by today's measures. Some, perhaps, seek immortality.
Cryobiology, Rabin assures, is about helping people. Now.
"We work on helping the quality of life, not on extending life," he says.
He was drawn to cryobiology from the start, intrigued by what he perceived to be enormous healing potential. Today, he's recognized as one of the field's pioneers. Just last year, he and his colleagues were awarded two sizeable grants, nearly unprecedented in the field of cryobiology:
The first came in September 2015 from the National Institutes of Health (NIH) in the form of $1.6 million to advance synthetic ice modulators (SIMs)–based cryopreservation. Rabin's team are working to protect biomaterials from the harmful effects of ice crystals during cryopreservation, which is devastating to cells, tissues, and organs, to the point that they can't regain viability and functionality after cryogenic storage. Rabin's team has coined the term SIMs, which belongs to a largely unexplored area of cryobiology development and research—SIMs represent a special class of compounds able to control the formation of ice crystals. The last thing anyone wants is ice crystals forming within human tissue being banked for future use—just as ice crystals will ruin a frozen steak, they'll destroy human tissue as well.
A few weeks after the NIH grant, the Department of Defense awarded Rabin and Mike Taylor, CMU adjunct professor of mechanical engineering, an additional $150,000 to develop technology for the cryopreservation of blood vessels, critical building blocks for organs. Taylor has also been a long-standing believer in the power of cryo, as those in the field call it; he's cofounder and chief science officer at Sylvatica Biotech and senior scientist at Tissue Testing Technologies, both based in Charleston, S.C., and he's focused on developing products and services that help improve the quality of cells, tissues, and organs with cryopreservation methods. Taylor's research has helped push the limits of hypothermia applied to surgery, enabling the human body to remain alive, or revivable, at extremely low temperatures to lengthen and facilitate procedures such as heart transplants.
He says he's thrilled to collaborate with Rabin: "Yoed is undisputedly recognized as the world's expert on thermomechanical stress in biological systems. To move forward, we need new tools, and he's very good at bringing to the table some new enabling technologies."
Although cryopreservation is very much still a work in progress, cryobiology has been performed in some form or fashion for ages. Rabin is well versed in its history: "The first written record of the use of low temperatures in medicine is recorded on Egyptian papyrus from 2,500 BCE. Then Hippocrates [who lived from 460 to 370 BCE] endorsed the use of cold to control bleeding and swelling. Robert Boyle [1627-1691] studied the effects of low temperatures on animals, and James Arnott used cryosurgery on cancer in 1845."
Cryosurgery is the flip side of cryopreservation: Cold is used to destroy. It was first applied to freeze unwanted superficial elements from the body, such as skin tumors or warts, and is widely practiced today worldwide. Russian reports on healing benign tissues like hemorrhoids is another example, which is essentially the destruction of blood vessels by freezing. As an invasive procedure, cryosurgery has been tested on virtually every organ in the body, such as the lung, liver, kidney, and prostate. Rabin is hopeful that one day these simple medical treatments will be more commonplace worldwide, which could lower the cost of healthcare. "Liquid nitrogen is less expensive than bottled water," he points out.
He began contributing to cryosurgery some 25 years ago. It's a field that he believes remains underutilized in many American hospitals, though he points out it has grown steadily as imaging technology has improved. Cryosurgeons depend on imaging from medical scans to determine where to place the cryoprobes, hypodermic needles fitted with a special cooler on the end through which the surgeon controls the cooling power of liquid nitrogen. Rabin has developed cryosurgery devices, temperature sensors, computer simulation techniques, and a computerized trainer for cryosurgery, and helped train cryosurgeons in workshops.
Owing to CMU's interdisciplinary tradition, Rabin says he often calls on colleagues to assist in the research that goes into the development of the surgical tools he has in mind. Among those colleagues is Jeyanandh Paramesh, who is a CMU professor of electrical and computer engineering. Rabin asked Paramesh to develop an integrated circuit, or chip, capable of wirelessly transmitting data from inside the body in real time, specifically to prevent cancerous tissue from escaping the insult of liquid nitrogen while protecting healthy tissue from being destroyed.
The chip Paramesh designed is about the size of a grain of rice, and an initial phase of this research to develop a sensing mechanism has been recently concluded with support by the NIH. Once funding is secured for the integration of the chip components, Paramesh expects clinical trials to follow. He's excited about the potential: "These chips offer an unprecedented level of control."
The number one killer in the United States is organ failure...we’ve only seen the tip of the iceberg of what organ transplantation can mean.
Although cryosurgery has been practiced for decades and is currently a common approach to treating prostate cancer, perhaps one of the reasons it hasn't become a go-to treatment option for other ailments is that it seems difficult to create a frozen region, often called the "ice ball," which perfectly matches with the shape of the tissue to be destroyed. For big tumors having complex shapes, creating such a match is currently an art, which requires significant training.
Successful cryosurgery applications do date back to the 1980s. Marsha Sawyer certainly needs no convincing of its efficacy. When she opted to have 13 cancerous tumors removed from her liver through cryosurgery in 1988, she was in no position to ask how accurate or controlled the procedure was. A mother with two toddlers at home, she had sought treatment from one of the nation's top liver specialists in New York City, as well as from cancer institutes across North America. She says she'll never forget what one of her doctors told her:
Go home; spend time with your kids so they have a memory of their mother.
She refused to accept the terminal diagnosis without a fight and took measures to bolster her immune system with a macrobiotic diet. But it wasn't enough to stop the cancer from spreading. She read about the pioneering cryosurgery treatment conducted by the physician Gary Onik and became his patient.
The surgery was performed by Onik at Allegheny General Hospital in Pittsburgh, a hospital committed to using cryosurgery to treat prostate cancer. It was there Onik and Rabin crossed paths in the 1990s, where Rabin served on the research faculty of Surgical Oncology. Very recently, Rabin has tested his cryosurgery training software at another unit of the Allegheny Health Network, the STAR (Simulation, Teaching, and Academic Research) Center. The objective of the training software is to shorten the learning curve of the new comers to the field of cryosurgery, while they benefit from the accumulated experience of leading surgeons.
Rabin has been particularly instrumental in improving cryosurgery pertaining to the quality of the instruments used in the procedure—their breadth, accuracy, and overall efficacy.
"I think there's a true kind of partnership that occurs between medicine and engineering in projects like this because you need an engineering type of association to get the best results," says Onik, who today is medical director for The Center for High Risk and Recurrent Prostate Cancer in Aventura, Fla., as well as a CMU adjunctprofessor of mechanical engineering "Yoed helped work out the parameters that were necessary to kill cancer well, and those are just critical."
One of the most remarkable outcomes of cryosurgery is the immunological response Onik has seen in patients thought to be terminally ill. In cryosurgery, the dead tumor cells are left in the body and removed through the body's natural detoxification process. As a result, a vaccination effect occurs, making the patient less susceptible to relapse.
"That's where we're going, and Yoed is right at the forefront of this," Onik says.
This is precisely what happened with Marsha Sawyer. Following her cryosurgery, she was able to return home to upstate New York, raise her two sons, and, to put it simply, live.
"I am definitely very seriously grateful for the work," she says, remembering all those she met for whom it was too late. She has been interviewed by the likes of CNN and The New York Times and considers it part of her life's mission to serve as a messenger for the benefits of cryosurgery. She views people like Rabin as true medical heroes. "It's nice to know there's someone out there still plugging away."
Plugging away he is.
Rabin has believed in the healing powers of cold for three decades, and it seems the rest of the world is starting to warm up to the idea, including the military. In 2015, a number of meetings were held around the nation addressing the potential for cryopreservation, among them a gathering at the U.S. Military Academy at West Point, N.Y., titled, "Organs on Demand: Vision-Setting Workshop on an Organ Banking 'Apollo Program' to Revolutionize Trauma, Transplant, and Regenerative Medicine."
Lt. Col. Luis Alvarez cofounded the Department of Defense's Office of Regenerative Medicine in 2014, and he says he's very much aware of what Rabin's research will mean once it can be implemented, particularly for mass-casualty situations: "What we have to deal with is combat injury, loss of tissue, how to sustain the viability of tissue, sustain life—all of these questions on how to keep tissue alive. Yoed is probably one of the world authorities on the understanding of this process."
Rabin continues to research how to best balance freezing something quickly while not damaging tissue. He's also exploring the flip side of this process—rewarming. Again, consider how food that has been thawed properly retains its natural texture and flavor far better than food that has been defrosted too slowly.
In order to preserve organs at sub-freezing temperatures, doctors require a solution that acts, for lack of a better term, like antifreeze but is nontoxic. Rabin and his colleagues aspire to make vitrification—freezing without crystallization—something hospitals and laboratories will be able to do routinely.
For example, a human heart can only survive on ice for three to six hours, but it's not really frozen. As a result, some 70% of viable human hearts, ripe for transplant, go unused, according to the most recent estimates from the Centers for Disease Control and Prevention. Sadly, lives hanging in the balance, waiting for an organ, are ultimately lost.
"The number one killer in the United States is organ failure," says Sebastian Giwa, who is cofounder and chair of the Organ Preservation Alliance "Published estimates [report] that more than one in three deaths could be prevented or delayed through on-demand access to organs for transplant—that's 1.5 times more lives saved than from curing cancer."
In the world of organ banking, Giwa and his team are considered a major catalyst, organizing global forums, laying the groundwork for new funding programs, getting the White House to engage and hold a roundtable on the need for organ banking, and connecting the necessary dots to make this concept a reality. In 2015, he organized the first global Organ Banking Summit on organ preservation and, in part, called upon Rabin's expertise for much of the program because he's "one of an elite cadre of experts."
"We've only seen the tip of the iceberg of what organ transplantation can mean," says Giwa, who is also cofounder, president, and CEO of Sylvatica Biotech, which is an organ banking R&D start-up. The waitlist for organs has grown exponentially in recent years, which accentuates the need to create safe organ banks. "Yoed has been a really, really key player in making that happen," says Giwa.
In the meantime, people like Jennings will have to bide their time. Just entering the prime of his life, he's acutely aware that he's much better off than those who came before him. Given how rapidly the field of cryopreservation is growing, he feels his time is better spent planning his wedding and adapting to life on the West Coast rather than worrying about how long his liver will hold out: "I'm counting on innovation and human ingenuity, which I'm actually pretty confident in, to one day ease my treatment."
It's someone like Rabin whom Jennings is counting on, a role Rabin embraces.
"I love science," says Rabin, "but if there's no use ... ." His voice trails off, leaving the rest of his thought unspoken. But its meaning is crystal clear.