Pigs with human hearts, and other wild tales from the future of organ donation

Organ donation is inherently unfair. There are a lot of people who need new hearts, kidneys, livers and lungs, and not nearly enough organs to go around. Even when they do become available, the place where you live can determine whether you receive a transplant in a few months or a few years. Such timing is often the difference between life and death.

“I think we should do away with organ donation,” one retired nurse I spoke with at a bioethics conference told me. “It can’t be done without manipulating people, anyway.”

She may have a point. Some people in the US game the system by putting their name on multiple state lists. Others turn to the global black market to procure a new organ from a broker. Both of these approaches tend to favor the wealthy at the expense of the poor. Still others have turned to social media to find a donor—an option that tends to work best for photogenic people with particularly sympathetic and heartbreaking stories.

In the meantime, an average of 22 people in the US die each day while waiting for organ transplants. In the European Union, an average 14 people on organ waiting lists die per day, and in India, 90% of all people on waiting lists die without getting an organ.

Now scientists are exploring a number of high-tech alternatives to obtaining organs from human cadavers. These options may one day solve the organ shortage problem—but they raise ethical questions of their own.

Pigs with human hearts

One option is to turn to the animal kingdom for cross-species organ donation—a process known as xenotransplantation. Xenotransplantation has a sordid history that can be traced back 17th century in France and England. The French doctor Jean-Baptiste Denis, for example, famously attempted human blood transfusions using the blood of sheep and calves. But as Dr. David K.C. Cooper notes in his history of cross-species donation, “the results were mixed.” France went on to ban human blood transfusions without the approval of the Paris Faculty of Medicine.

 The animal needed to be kept alive and strapped to the human recipient for a few days, until the human’s blood system incorporated into the donated skin.  Cooper explains that in the 19th century, several scientists tried animal-to-human skin grafts using sheep, rabbits, dogs, cats, rats, chickens, pigeons, and frogs. Pedicle skin grafts, or grafts that included blood vessels, were particularly troublesome because the animal needed to be kept alive and strapped to the human recipient for a few days, until the human’s blood system incorporated into the donated skin. Then the animal’s skin would be cut off from the animal donor. While some of the grafts may have worked temporarily, Cooper writes that it’s likely that none became permanent. The 20th century saw continued efforts at xenotransplantation, including chimpanzee-to-human kidney transplants in the 1960s and an unpopular attempt to transplant a chimpanzee heart into a dying human patient in 1964.

In the present day, animal-to-human organ donation is making a comeback thanks to the gene editing system CRISPR/Cas9. Pigs are the animals best suited to cross-species organ donation, since they’re easy to breed in captivity and their organs are the right size for humans. Thanks to CRISPR, researchers have been able to edit some of the problematic portions of the pig genome to make it more acceptable to the human immune system, inactivating retroviruses that could infect human hosts and genes that could lead to blood clotting in humans.

Thus far, scientists have only been able to graft pig hearts into baboons—but researchers appear to be making progress. One recent study published in Nature Communications reported that baboon hosts survived a median of 298 days, up from the previous median of 180 days. One baboon even lived to a record 945 days.

 Scientists are experimenting with planting human stem cells into pig embryos in the hopes of growing hearts and livers. The other option is to grow human organs inside a pig’s body. Scientists are experimenting with planting human stem cells into pig embryos in the hopes of growing hearts, livers and other body parts that could be used for transplants. According to MIT Technology Review, researchers in the US brought about an estimated 20 pregnancies of pig-human and sheep-human chimeras in 2015, although none of the chimeras were brought to term.

Scientists have already successfully managed to genetically modify pig embryos so that the fetal pig lacks a heart or other organs or tissues. Their hope is that, by injecting human stem cells into the embryos, they can prompt human cells to create the missing organ. Cardiologist Daniel Garry tells the MIT Technology Review that he has successfully experimented with this approach by injecting the stem cells of another pig into the genetically modified embryo. The US Army recently awarded Garry a $1.4 million grant to continue his research on growing human hearts in swine.

 It’s one thing to create a pig with a human liver; it is quite another to make a pig with a human brain. These chimeras are not without controversy. Pope Francis reportedly approved their creation, but the National Institutes of Health announced in 2015 that it would not fund research involving human-animal chimeras until they have reviewed it further. The concern is that these experiments might blur the lines between human and animal—particularly if the animals grow human brain cells. As NIH ethicist David Resnik told MIT, “The specter of an intelligent mouse stuck in a laboratory somewhere screaming ‘I want to get out’ would be very troubling to people.” How many human organs does a pig need to have before it is considered more human than not?

There are also ethical considerations about what kinds of organs are all right to grow inside pigs. It’s one thing to create a pig with a human liver; it is quite another to make a pig with a human brain. Margaret Atwood took the implications of this to a disturbing extreme in her speculative fiction trilogy, Madd Addam. Her Pigoons were pig-human chimeras whose pre-frontal cortex made them as intelligent, and as cunning, as humans. Today, the concept doesn’t sound so far-fetched.

Print a lung

These days, 3D printing is being used in the medical field to make scaffolds, prosthetics, and bone implants. So why not try to make biological parts?

Scientists at institutions including Stanford University and the Wake Forest Institute for Regenerative Medicine have been working on using 3D printers and stem cells to create human organs. As long as the printers use stem cells from the patient, these organs would theoretically pose little risk of being rejected by their immune system.

But there are some complications. Our bodies naturally deliver oxygen and nutrients to cells using an intricate network of blood vessels. Reproducing this network has been a barrier to making 3D-printed organs, which need oxygen and nutrients, a reality.

However, several research groups have made headway using a nanomaterial that melts at odd temperatures, called hydrogels. One research group creatively combined hydrogels with a cotton-candy machine to make micro-scale capillaries that are the same size as blood vessels.

 Some bioethicists suggest that 3D-printed organs could give people license to engage in destructive behavior. At this point, scientists have not been able to make human-sized, 3D-printed solid organs. But they have been able to print tissues with multiple cell types, including the blood vessel network and the extra cellular matrix.

If scientists are eventually able to make 3D-printed organs, we’ll inevitably run into some unique dilemmas. What if the manufactured organs function more efficiently than the original? An up-and-coming athlete who doesn’t have the lung capacity for endurance sports might want to trade in her old lungs for a 3D-printed set. But would that give her an unfair advantage over her competitors?

Alternatively, imagine aging athletes replacing their old tendons with brand-new, springy ones. The line between enhancement and therapy is ambiguous here. The sports community already regularly confronts these kinds of ethical issues. Tommy John surgery, which takes a tendon from the arm or leg and replaces a worn-out ligament in the elbow, is understood as therapeutic and is therefore considered legal in baseball. But human growth hormones are categorized as performance enhancers and are banned by the World Anti-Doping Agency.

In addition, some bioethicists have suggested that the rise of 3-D printed organs could give people license to engage in destructive behavior. Why not smoke a pack a day if you can print new lungs, or give up on binge-drinking when you can easily get yourself a bright and shiny liver?

Organs with an off switch

Mechanical organs are already available today—but they are typically a stopgap until an organ becomes available. Researchers have yet to make a completely self-contained mechanical heart for long-term use à la Ironman. However, they are getting closer.

The manufacturer SynCardia, for example, has developed a fully-functioning artificial heart approved by the US Food and Drug Administration for patients waiting for a transplant. The company hopes to receive FDA approval to use the device as a permanent solution. One of SynCardia’s patient lived four years with a mechanical heart until he finally received a donor organ.

 Researchers have yet to make a completely self-contained mechanical heart for long-term use à la Ironman. However, they are getting closer. Carmat, a company in France, is also working on a long-lasting mechanical heart that is in the early stages of clinical trials. Unlike SynCardia’s bulky power pack, which patients have to carry in a backpack or shoulder bag, Carmat’s clips onto a belt worn around the patient’s waist. Carmat’s model is also made with a layer of cow-heart tissue to help the mechanical device integrate into the patient’s body.

While long-term mechanical organs are still on the horizon, we can already anticipate some of the ethical questions they raise. Many people already have pacemakers and left-ventricular assist devices (LVADs). Pacemakers can restart the heart if it stops beating, while LVADs can take on a large portion of the heart’s workload for people who have ventricle failure. In effect, these devices give hearts an “off switch.”

One small recent study, published in JAMA Internal Medicine, highlighted the problems that such an off switch can raise. Eight caregivers who had lost a loved one with an LVAD device reported that they were unprepared and uncomfortable with turning off their loved one’s LVAD as he or she approached death. They were unsure about how the LVAD would impact the process of death and what was legally and ethically permissible when it came to turning off the device near the end of life. Several of the caregivers viewed turning off the machine as akin to suicide, and one caregiver even viewed it as murder. All of them found it disconcerting to turn off the LVAD.

These innovations in gene editing, stem cell research, 3D printing, and biomechanics may eventually provide desperately-needed solutions to the organ crisis. If we want to be ready for that day, it’s important to begin debating ethical considerations well in advance. We should start thinking now about where we draw the boundaries between life and death—and even how we define what it means to be human.

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