In recent months, transplanting organs from pigs to people has been increasingly successful. The pigs used as the source of the organs have been genetically manipulated to make their kidneys, hearts, and other tissues acceptable to human recipients. Their genes have been altered to keep the human immune system from attacking the animal organs and destroying them.
Until a few months ago, transplants from pigs to people were generally restricted to taking an organ, such as a kidney, from a pig whose genes had been altered from conception and placing that organ in a ‘brain-dead’ human. The failure of the pig organ would be of no consequence to the recipient since survival or continued support in the setting of brain death is not generally considered ethical. Without brain function, an individual is considered legally ‘dead,’ and if his or her heart and other organs do not fail over the course of days or weeks, life support is usually withdrawn. Recent transplants of genetically altered pig kidneys into brain-dead humans have shown good renal [kidney] function for weeks or months. Having realized some success with kidney transplants, investigators have attempted pig-to-human heart transplants. Unlike the recipients of the pig kidneys, the recipients of the pig hearts have had healthy brains.
The only heart transplant candidates eligible for modified pig hearts are individuals who are ineligible for a human heart and who will die in the near future without a heart replacement. There are a variety of conditions that make people with heart failure ineligible for a heart transplant from a human donor. Obviously, the human donor must himself or herself be brain-dead to be considered a heart donor. In September, 2023, a patient at the University of Maryland Medical Center received a genetically modified pig heart. After more than a month from the procedure, the heart appeared to be doing its job, and the recipient’s body had made no substantial efforts to reject [destroy] it.
A prior attempt at pig-to-human heart transplantation in January, 2022, failed. A genetically modified pig had also been used in that trial, but the recipient died after just two months from the date of the surgery. His death was attributed to a pig virus that apparently had been transplanted along with the heart. There were no substantial signs of organ rejection in the man receiving this pig heart.
The pigs providing the hearts in these experiments had ten genes altered while they were nothing more than fertilized eggs. Three pig genes were silenced, one pig gene was modified, and six human genes were added. The two men who received the modified pig hearts were treated with drugs to suppress their immune system’s rejection of foreign tissue, but the limited experience with these two people indicated that the pig hearts elicited none of the lethal rejection activity that a conventional pig heart would evoke.
If further success with genetically modified animals establishes the feasibility of pig-to-human organ transplants, the struggle to meet the demand for organ transplants may be over.
Nature itself has modified genes in many species over the course of thousands and millions of years. This has been the basis for evolution and the origin of new species. One of history’s many ironies is that Charles Darwin [and other less famous biologists] recognized the incremental changes in nature that led to new forms of life. He described the phenomenon of evolution in his landmark book “Origin of Species.” At the same time Darwin was collecting material for his book, an Austrian monk, named Gregor Mendel, was studying pea plants in his garden and recognized patterns in the inheritance of flower colors and other plant characteristics, patterns that became the basis for the study of genetics. While Darwin pondered how changes in living things led to new species, Mendel sent him a copy of his publication in which he described the mechanism involving recessive and dominant “Merkmalen” [i.e., traits that proved to be what we call genes] that would explain what Darwin had observed. Darwin never read the correspondence from Mendel and never figured out the mechanism underlying evolution.
One of Nature’s most successful genetic experiments, from a human point of view, was the transformation of the ancestors of wolves into dogs. Before selective breeding by people led to giant mastiff hounds and diminutive chihuahuas, a few ancient wolves appeared with less of the aggressiveness and viciousness typical of their species. The genetic basis for this transformation was a deletion of genetic material that made the ancestors of grey wolves unfriendly to humans. Losing bits and pieces of relatively few genes made a notoriously dangerous [from a human point of view] animal into ‘man’s best friend.’ Dogs were the first animals to be domesticated and remain the most popular nonhuman companions for people all over the planet.
The animals that diverged from the ancient wolf lineage to become the more friendly creatures we have labelled ‘dogs’ may have chosen to affiliate themselves with Homo sapiens [man] because of our culinary habits. While people were still hunter/gatherers, they provided left-overs which included bones and other hard to chew or unpalatable animal remnants that appealed to the carnivorous canines. Over thousands of years, these camp-following dogs may have been selected by their human benefactors for their ability to follow human cues, spoken or otherwise. Some of the dogs hanging out at the human encampments could have alerted humans to unwelcome guests nearby or exhibited a talent for motivating domesticated animals to stay in herds.
Their numerous special talents have been cultivated by humans, but the basis for our enduring relationship with dogs is that they chose us. They learned to tolerate us and profit from their interactions with us. They chose not to bite the hands that fed them and developed mutually beneficial relationships with people that have endured for thousands of years. In dealing with our fellow humans, we have much to learn from dogs.
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 U.S., as well as in England, Germany, and France.