When it comes to organ transplants, the intestine has historically been off-limits. Unglamorous and, until recently, unsuccessful, intestinal transplants are complicated and difficult processes. The first successful transplant of a portion of the small bowel was performed less than 25 years ago, in 1989, and even today the preferred treatment for irreversible intestinal failure is total parenteral nutrition, or TPN, which calls for intravenous feeding rather than transplantation.
After the innovations of four Yale students, however, the future of small intestine transplants is beginning to look slightly less grim. Offered last fall, “MENG 404 – Medical Device Design and Innovation” gave students the opportunity to address some of the most pressing issues in modern medicine, including intestinal transplantation. The class is designed to integrate medicine, engineering, and finance by tasking students with designing, assembling, and testing a working prototype of an invention that addresses a current problem in medical treatment. In just 15 weeks, the class has produced four examples of groundbreaking technology, one of which is the Small Bowel Perfusion and Transportation System. If you look past the hazard markings and the medical warnings, the device looks like a cooler you might bring to the beach.
With the help of professors, students were allowed to strike out for themselves and develop innovative projects from conception to construction. In addition to this guidance, a dozen guest lecturers ranging from physicians to industry professionals and entrepreneurs visited the class to offer their own perspectives.
“On day one, we had no idea what we would end up with, the only thing we knew for certain was that we had 15 weeks to get there,” said Dr. Joseph Zinter, who helped organize the class. Zinter was one of two instructors who created the class, developed the curriculum, and met with students in weekly advising sessions. Doctors from the medical school identified four major areas that they felt student innovation could invoke tangible change, and passed these ideas along to Zinter. Natalie Pancer SM ‘14, Andrew Crouch TC ‘14, Brian Loeb SY ‘14, and Raja Narayan MPH ’14 set out to tackle one of the most difficult problems in transplant science.
Historically, intestinal failure has amounted to an unpleasant and prolonged death sentence. Abdominal trauma or disease can cause damage to the intestines that render large portions permanently inert, or require removal for the immediate survival of the patient. Until the 70s, patients who pulled through these operations were not able to take in food and inevitably died from starvation.
In 1968, TPN was developed in order to prolong the lives of those suffering from major intestinal failure. A machine is hooked up to a patient for 10-16 hours a day and pumps nutrients directly into the bloodstream, allowing the body to remain nourished despite its inability to process food ingested orally. This machine can now be carried in a backpack, its physical presence reduced so that it is as minimally invasive to the lives of patients as possible. Even so, those who use the device often suffer from depression due to the limits TPN places on their lives; infections and blood clots can develop from constant use of an IV needle. Perhaps the worst side effect, however, is the constant, unrelenting hunger. The body primarily registers hunger using the mouth and the stomach, so when it is fed only via the bloodstream, the sensations of tasting food and feeling “full” are lost. Even though the body is receiving nutrients, many patients constantly feel pains as though they were starving. Roughly three quarters of those receiving TPN survive for more than three years. For the 30 percent for whom TPN fails, intestinal transplantation is recommended as a last-ditch measure.
The fragile nature of intestinal tissue leads to high death tolls and complication rates of intestinal transplants, both of which are markedly higher than those for heart, liver, or kidney transplants. “The intestine is a very delicate tissue—it’s layered with muscle, mucosa, connective tissue, and it’s also very brittle outside the body when it’s not receiving nutrients,” said Raja Narayan, MPH ’14, master’s candidate in public health and a student in the course. The organ’s composition makes the process of removing, transporting, and eventually transplanting it an intricate and often rushed task. Blood and nutrients constantly flow through the body, and in the absence of this continually fluid, the intestine begins to deteriorate as it uses up available resources and begins to accumulate waste.
The complexity of the task is exacerbated, paradoxically, by the advancement of medical science. Through relatively new medical techniques, the surface area of the faltering intestine can be extended so that, even as it fails, it continues to absorb nutrients far longer than it might on its own. Although this procedure prolongs the functionality of the intestine, it also means that patients in dire need of transplants are sicker than ever before, requiring any potential transplanted tissue to be of “pristine” quality, Narayan said.
Unlike hearts or kidneys, intestines are quickly rendered useless on cold operating tables or in buckets of ice. The vast and intricate network of capillaries responsible for delivering blood and nutrients to the 23-foot long stretch of tissue becomes inert, and as soon as the organ is removed from the body it begins, slowly and inexorably, to die. In an already weak patient, the consequences can be severe. Only two-thirds of intestinal transplant recipients live for more than three years.
The survival rate would be far better, the four Yalies thought, if an intestine could be preserved outside the body.
The Small Bowel Perfusion and Transportation System (otherwise known as the Intestinal Preservation Unit, or IPU) created by this team of students in MENG 404 works to slow the death of an intestine outside of the body. The system uses the organ as tubing to connect intake and output valves, while a nutrient solution constantly runs through the intestine. This solution keeps the intestine supplied with the necessary components to prevent organ death, while simultaneously preventing harmful waste products from building up over time inside the intestine. Narayan is hopeful that the machine will solve many of the problems that have made intestinal transplantation exceptionally difficult.
Students were given the green light to attempt a trial using pigs, and the organ experienced far less degradation when using the IPU than when using typical organ preservation procedures, which amount, Narayan said, to “throwing the intestine into a bucket of ice in a plastic bag” and hoping for the best. He is optimistic that results will be even better in human trials not too far in the future. “Fortunately, the procedure is much easier in a human than in a pig,” he said. Whereas a pig’s intestine is seemingly endless at 75 feet long, a human’s stretches only 23 feet. “We had to cut the tissue, introducing an artificial change in the tissue, so going forward we expect it to be far simpler in humans,” Narayan said.
Students are currently preparing an oral presentation for the Society for Surgery of the Elementary Tract, a national organization committed to advancing surgical procedures for digestive diseases. Rather than focusing on theoretical issues, MENG 404 allowed students to immediately connect their work to real problems and tangible applications. “We might not have gotten to experience [this type of work] until 20 years after medical school,” Narayan said. In less than a year, this class has allowed an abstract idea to turn into a functional prototype that could potentially save hundreds of lives and improve the quality of life for thousands.
MENG 404 is a new breed of class at Yale, representing a fervent commitment to applied science, engineering, and technology. Though students and instructors considered the class to be an unremitting success, the class markedly departs from the university’s classic liberal arts ethos at the heart of the institution.
Zinter hopes that model courses like MENG 404 may serve as an example for proponents of this shift. The integration of multiple fields, the process of continual questioning and reevaluation, and the active discussion between students and professors provide students with the opportunity for broad-based intellectual development in an increasingly science-oriented world. The scientific experience of MENG 404, defined by creativity and participation, extends beyond the typical Yale student in the sciences, one often defined by vast, inaccessible lecture halls. Only a small portion of students has begun to access science through a more interactive manner.
According to Dr. Zinter, MENG 404 accepted 20 of the 50 applicants for the course. In addition to the two professors overseeing the course and the 12 guest lecturers throughout the year, each of the four groups met weekly with one to three professors who were particularly knowledgeable about their specific projects. While it is commendable that so many people and so much passion have been invested into this course, these students are only a small fraction of those taking science and engineering courses at Yale. It’s hard not to wonder what the other 30 students who applied for MENG 404 might have come up with.