Liver transplants got some attention recently thanks to Netflix’s House of Cards. When President Underwood needs a liver transplant quickly, his staff makes underhanded arrangements to bump him to the top of the list. It’s a compelling plot point because many people die while waiting for a donor liver. But is this portrayal of organ transplantation realistic? And would Underwood’s liver transplant even be possible without animal research?

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Fictional President Frank Underwood received a liver transplant. (Image Courtesy of Wikipedia)

Animal Research Behind Liver Transplants and Immunosuppressive Drugs

Seven thousand liver transplants were performed in the U.S. in 2015 alone, and fifteen thousand people sit on the waiting list hoping to qualify for a new liver. It’s the second most common type of organ transplant after kidneys, making up almost a quarter of all organ transplants. Chronic illnesses of the liver and bile duct are the most common diseases necessitating liver transplants. Hepatitis, cirrhosis, fatty liver disease, and autoimmune diseases can destroy the liver’s function, making a transplant a patient’s only hope for survival.

The first human liver transplant was performed in 1963, and the procedure remained experimental through the 1970s. Patients rarely survived a year post-transplant, often dying of graft-versus-host disease after immune cells in the donor organ damaged their healthy tissues. The introduction of potent immunosuppressive drugs such as Cyclosporin A and Tacrolimus in the 1980s and 1990s improved outcomes considerably, giving recipients about a 60% chance of living for 15 years post-transplant. Cyclosporine and Tacrolimus, along with dozens of other specialized anti-rejection medications, were approved for human use after years of careful animal research. Immunosuppressive drugs radically changed the game, making organ transplants a viable long-term treatment for many diseases.

Even now that transplants are more commonplace, animal research is contributing to advances in transplant techniques and technology. In labs all over the world, rats and other animal models are helping researchers find ways to improve immunosuppressive drug delivery and minimize their dangerous side effects to other organs, including the kidneys.

The Donor List

Human liver (Courtesy Wikipedia)

Despite the fascinating machinations and power plays utilized to move Frank Underwood to the top of the donor list, tampering with the organ transplant list is next to impossible. A complex computer algorithm determines each person’s position, and as donor organs become available locally, donor information is then matched to eligible candidates. Medical urgency, length of time on the waiting list, and compatibility of blood type and genetic markers are the main criteria by which organs are matched. If a local match isn’t found immediately, the search expands to nearby regions, but the timeline is tight: a donor liver can only last 12 hours in storage before it degrades too much to be used. So while, the House of Cards portrayal of the donor list is fiction, the storyline highlights an important problem: there are many people who need a liver transplant and won’t get one. That’s where animal research one again will save the day.

Animal Research Continues to Deliver Transplant Breakthroughs

Researchers are working towards better ways of preserving organs awaiting transport, to keep them viable for longer. Rat research has led to new methods of freezing organs without causing cellular damage. Organs can be perfused with a concentrated sugar solution that prevents formation of ice crystals in the delicate cells, in a process called supercooling. In a study done in 2014, scientists were able to slowly cool donor rat livers using the technique, freeze them for three days, and then thaw and transplant them. The control group received livers that were stored for three days using current storage techniques. The rats that received the super-cooled livers lived months longer post-transplant than the control group. Three days of viability will make it possible to ship organs farther and to where they’re most needed.

Taking the opposite approach, other researchers are working on ways to preserve organs at body temperature instead of freezing them. Experiments with pig livers showed that perfusing the donor organs with warm blood (normothermic perfusion) instead of a cold nutrient solution led to better retention of liver function. A liver connected to a normothermic perfusion machine can actually continue to produce bile, which is key: if the bile stops circulating in the stored liver, it can cause irreversible damage and make it unsuitable for transplant. The normothermic method, like the supercooling technique, can potentially extend the storage time to three days. The first human trials using this preservation method took place in the UK in 2013 and the results are promising.

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(Image courtesy Tareq Salahuddin)

Any research that lengthens the viability time of a donated organ will help more people find a match and get off the transplant list. There’s even a good chance that longer storage times will mean better transplants with less rejection. A good tissue match is essential if an organ is to be accepted by the recipient’s body, but sometimes the medical team has to settle for a “close enough” match. If the supply of donated organs is more reliable because they can be stored longer and shipped farther, then doctors can afford to be more selective about the matches. That will make for safer transplants, and so many more lives saved. Animal research has played a major role in the development of organ transplantation and anti-rejection drugs. Today, it is helping researchers refine transplantation methods and technology to make the procedure ever more successful. And despite Frank Underwood’s ruthless ambition and morally suspect political schemes, we’re delighted he lives on for another season. We have Netflix and animal research to thank for that!

 

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