50 years after the first heart transplantation–The dawn of a new age in medicine

Around 5000 hearts are transplanted worldwideeach year. The procedure belongs to the standard repertoire in clinical surgery today. It all started exactly 50 years ago. It was the medical coup of the century, when on December 3rd, 1967 the South African surgeon Christiaan Barnard succeeded in being the first to effectively transfer a heart from one human to another. Barnard transplanted the heart of a young woman who had died in a traffic accident the day before into the chest of 54-year-old Louis Washkansky. Some later called this “the moon landing of medicine”, others the most controversial operation in the history of medicine.

Barnard achieved the status of a publicly worshiped magician and pop star, was present on the boulevard tabloids of the world, and was the second most prominent South African after Nelson Mandela (andfrom then on focused his life on affairs, money and fame). However, before the procedure he was by no means theexpert in the field, that he was described as afterwards. He had previously performed only a few experiments with animals, and even thesewith little success, and had been anything but a pioneer in the field of transplantation medicine. Physicians who had much more experience with transplanting organs in animals were shocked by Barnard’s operation, that someone who had hardly performed any research in the field of his own had the courage or the impudence to undertake such an endeavor.

And Barnard did not work without fault during his epoch-making intervention. Already during the surgery, he made a fatal mistake that nearly ended his patient’s life before the actual transplantation. Afterwards Washkansky survived only 18 days before succumbing to pneumonia. The pathogens of the deadly disease were able to spread so quickly only because Barnard had the immune system of his patientvehemently suppressed by drugs, as he assumed that the new heart would be acutely rejected by the body – which turned out to be incorrect. Barnard’s famous surgical procedure hardly gave his patient a longer life than he would have had with his own sick heart. The effects on clinical surgery, however, was tremendous: What followed within 12 months of Barnard’s procedurewas, as the New York Times put it, “an epidemic of heart transplantations”, with about 100 operationsworldwide. The real experts now also dared to perform the operation. Sometimes it just takes such courage for technical progress to take concrete shape, or just that portion of craziness, Barnard undoubtedly displayed. Today it is even possible for people with donor hearts to run a marathon or climb Mount Fuji in Japan.

Almost to the day 15 years later began the era of artificial hearts: On December 2, 1982 the first permanent artificial heart was implanted into the body of the American Barney Clark atthe University Hospital of Utah. Today artificial hearts are often used for patients with heart disease as a bridge until a donor heart becomes available. Meanwhile, patients can survive with them for up to five years and more. Sometimes, during this time, the heart of the patient can recover with the help of the artificial heart sufficiently well that it becomes fully functional again and the artificial heart can be explanted.

However, the hopes of the doctors go much further: they are already dreaming of breeding organs. With the help of stem cells, they are looking for ways to make the recipient’s body more tolerant of a stranger’s heart without having to suppress the immune system. With this, even the transfer of other species’ organs, the so-called xenotransplantation, could soon be ready for practical applications. The best candidates for animal organ donation are believed to be pigs. They are readily available, their organs are anatomically comparable to those of humans, their hearts are equally powerful, and new infectious agents are unlikely to become an issue, as pigs have been in close contact with humans for many generations. Scientists are currently researching genetically modified pigs so that their organs are no longer recognized as foreign by our body.

But researchers worldwide are already working oneven more dramatic alternatives: Biologists and doctors pursue the goal of creating replacement organs from scratch. This idea is by no means new. Already more than a hundred years ago, zoologist Ross Harrison cultivated nerve cells outside the body which continued to grow. In 1972, Richard Knazek and his team grew mouse liver cells on hollow fibers. And just ten years later, burn victims were transplanted skin that had previously been bred from their body’s own cells. In 1999, it was possible for the first time to grow nerve cells from mouse embryonic stem cells. When these were insertedinto other mice, who were suffering from a type of multiple sclerosis, the animals recovered fully.

With this “tissue engineering”, physicians have another powerful method at their disposal. In practice, its concrete application could be as follows: Differentiated cells are removed from the donor’s organism and multiplied in the laboratory in order to then replace diseased tissue in the patient’s body. The problem with this method are the body’srejection reactions that still occur. This is where the stem cells come into play. First, the patient’s adultstem cells, i.e. non-embryonic cells and thus cells that are also present available in adults, were used for tissue engineering. The advantage: Tissue grown in this way is not classified as foreign and thus not rejected by the patient’s immune system. Adult stem cells are multi- but not totipotent, for example, an adult stem cell from the skin can generate all cell types of the skin, but not a liver cell or a blood cell. An important next step was taken in 2006 with the creation of “induced pluripotent stem cells” (iPS): Scientists from Kyoto transformed adult stem cells back into their embryonic state. In contrast to adult stem cells embryonic stem cells are pluripotent, i.e. they can differentiate into all sorts of body cells. Any tissue can thus be bred from the iPS all-rounders – tailor-made for the patient from whose body the original adult stem cell originated.

Stem cells could also be used for another technique of tissue engineering: Here the DNA is removed from a donor organ leaving behind the collagen scaffold of the organ, which is then colonized by the patient’s stem cells. It is as if the old inhabitants were driven out of a block of flats and new tenants take over the empty apartments. In joints, urinary bladder, skin, or ureter such a production of “patient-owned” tissue has already been achieved. The collagen scaffold can even be formed in the laboratory, a donor organ is then no longer required. In this way, the Wake Forest Baptist Medical Center for Regenerative Medicine in North Carolina succeeded in creating artificial vaginas that were successfully implanted into patients. Theoretically, these women can even have children. Artificial penises from the laboratory are also in the testing phase.

We can also print body organs already. This is performed on the basis of a small tissue sample and a 3D image of the corresponding organ. With the body’s own “ink cells” which are produced from stem cell cultures the organ is built up layer by layer (in the 3D printing terminology, one also speaks of “rapid prototyping “). Today, hip bone and foot bone implants are producedbysuch 3D printers with aprecision that was imaginable just a few years ago. In May 2017, researchers from Northwestern University in Chicago even announced that they had been able to produce functional ovaries of mice by3D printing. Three out of seven mice thus gave birth to healthy and reproductive offspring. “The techniques developed here are the necessary first steps to validate the significant undertaking of exploring such an approach for creating a human bioprosthetic ovary,” the researchers stated in their report.

Nothing speaks against a future development in which entire body parts, including internal organs, are routinely modeled and printed or bred outside the human body. Future medical advertisements could thus read as follow:

• “You no longer want insulin injections for your diabetes? We’re going to breed you a new pancreas.”
• “Parkinson? We grow you new nerve cells. “
• “Paraplegic after an accident? We will breed you a new spinal cords.”
• “Heart failure? We willprint you a new heart.”

What has so farbeen familiar only to science fiction fans, could today, only 50 years after the first heart transplant, become reality much faster than most people can imagine.