A pig’s heart was transplanted into a human last week. Whether this is the first of many such transplants or an isolated case will become evident within a few months. The heart recipient was 57 years old. Why he was not considered to be a candidate for receipt of a human heart was not revealed. It may have been that he was at risk of dying too soon to wait for a suitable heart or he had a terminal illness that would have made transplantation of a human heart futile. Human hearts worth transplanting are in short supply. Pig hearts are numerous. We kill millions of pigs every year for bacon, egg, and cheese sandwiches.
The human immune system protects us from infections by attacking and destroying germs or infected cells, but it will also aggressively attack and reject tissue transplanted from an ordinary pig. The pig from whom this heart was taken had been genetically modified. Several genes were ‘knocked out,” that is, silenced, and a few others were inserted into the pig’s genetic material in an effort to make the heart tissue look more human. Simply put, the gene changes were meant to enhance acceptance of the heart by the human immune system. The lucky recipient of this heart was also placed on drugs to suppress his immune system, just in case the medical magic of gene manipulation failed. That this will work is unlikely. If it all succeeds, the people who came up with the ideas may win Nobel Prizes. If it fails, the people who came up with the ideas will probably say it was someone else’s idea.
Innovative approaches to medical care, such as this pig-to-human-transplant, often require the input and cooperation of numerous physicians and scientists. Unfortunately, the expertise of one group may not extend sufficiently to another group to allow for a successful collaboration. With this transplant attempt, enough pig genes need to be inactivated and enough human genes need to be inserted to get this man’s immune system to be fooled or at least to be complacent. This man’s immune system needs to accept the pig heart as if it were not just a human heart but in fact his real heart.
Each of us has surface markers on our cells that are almost as unique as our fingerprints. Unfortunately, the pig heart has its own surface markers on its cells that make it unique and clearly nonhuman. Without changes to or elimination of those identifying markers, a pig heart placed in a human chest would be attacked by the human immune system as rapidly and as irrevocably as if it were a monster from a sci-fi movie (see “Alien“). In the pig-to-human scenario, the pig heart would be killed, and its human recipient would die from heart failure.
Getting some one else’s or some thing else’s markers to match those produced by the genes of any specific individual has been virtually impossible. If this man’s immune system is not convinced that the heart placed in his chest is a duplicate of the original heart, the one that failed and needed replacing, it will attack and destroy the new heart. Since getting the immune system to accept a transplanted human heart from an unrelated human donor has been exceedingly difficult, one must assume that the odds of getting this 57 year old man’s immune system to not attack the genetically modified pig heart are long.
A wise pediatrician once noted that the best way to manage a premature infant is to keep it from being premature. Similarly, the best way to manage heart failure is to keep the heart from failing. Heart transplants are a dangerous and often unsuccessful option in situations where strategies to protect the heart have failed. It has grown into a multibillion dollar industry. The cost of each heart transplant, including all testing, medications, surgical fees, hospital costs, and postoperative therapies, ranges from $1.3 to $1.7 million. About 18 % of heart transplant recipients will not survive a full year after the surgery. Considering the probability of dying without the surgery, a one-year survival rate of 82% is good but hardly formidable. Hospital managers are, nonetheless, eager to have transplant services in their institutions. The procedures involve large sums of money, enhance the hospital’s prestige, and involve relatively little risk of litigation, given the tenuous condition of most of the transplant recipients and the complexity of the procedures performed.
The principal restriction on the number of heart transplants performed in the United States is the limited supply of healthy, donated hearts. Suitable hearts for transplantation are generally harvested from individuals who have been declared ‘brain dead’ as a consequence of massive head trauma or bleeding into the brain. Problems that destroy the brain but leave most other organs intact are fortunately relatively rare. The infrequency of this tragic situation limits the supply of organs for transplantation. That is why transplant centers have turned to the pig for a limitless supply of organs that are similar to those found in humans.
And so this was the challenge for the pork-loving transplant team: they needed to change the genes in the donor pig to make its organs look human, at least to the extent that would fool the recipient human’s immune system. Of the pig’s 22,000 genes, the geneticists involved altered fewer than a dozen genes. The immunologists following the patient after the transplant placed him on medication to weaken his immune system, just in case the gene modification was not sufficient to keep this man’s immune system from killing the pig heart. This approach has the disadvantage of making the immunosuppressed man more vulnerable to infections that might kill him. If this nonetheless succeeds and the partly porcine man survives more than a few months, we shall have entered a new era for organ transplants. If it fails, the men and women involved in the effort will have a better idea of what does not work and shall try again. America may yet come to love the pig as something more than a source of breakfast meat.
Dr. Lechtenberg is an Easton resident who graduated from Tufts University and Tufts Medical School in Massachusetts and subsequently trained at The Mount Sinai Hospital and Columbia-Presbyterian Medical Center in Manhattan. He worked as a neurologist at several New York Hospitals, including Kings County and The Long Island College Hospital, while maintaining a private practice, teaching at SUNY Downstate Medical School, and publishing 15 books on a variety of medical topics. He worked in drug development in the USA, as well as in England, Germany, and France.
