A natural wonder informing modern genetic miracles
By: A’liya Spinner
A Farm for the Future
The livestock facility at BioLife Farm is warm and well-ventilated, even in deep winter. Though several feet of snow outside prevent the furred inhabitants from wandering the pasture beyond their barn, they have room to roam in their pens full of hay and enrichment objects. All manner of farm animals live here, including stout, oddly-proportioned piglets nearing a year of age. In several weeks, they will give their lives— not for pork, but for the life-saving human organs they grow inside them. They contain mostly kidneys, though some are separated in a pen of future hearts or livers. For now, however, they live happily, pushing toys around their straw bedding in good spirit and health thanks to frequent checks by veterinarians.
Beside the pigs are grown lively goats. A farmhand who has spent the last few months learning the personality of each one wades between the herd, stooping to collect blood samples with a quick jab that most of them do not notice. They trust him, and follow without complaint when his handheld sampler informs him an individual is ready to donate. With a slice of apple, he leads them down a row of pens and to a machine designed to be comfortable for the animal, cushioned and heated. Practiced from years of living at the facility, his chosen goat kneels and is secured in place by straps; it does not care, and contentedly chews the sugary treats that have been placed before it to distract from the process. The farmhand uses numbing spray on its haunch before carefully sliding a needle into the goat’s vein; he tapes it down and steps back as the machine’s tubes begin to fill with blood. But this is not goat blood that the animal is donating— instead, it is a living donor for the human blood produced by its own body. It will hardly notice the loss, returning to its pen within ten minutes from sitting down, and won’t be drained again for at least a week. Healthy goats donate healthy blood, and have become an indispensable resource for hospitals across the nation.
While the donor-goat lazily chews, the farmhand walks between the rest of the pens, scanning for signs of distress or disease. The BioLife facility does not raise any animals for meat consumption, an increasingly novel concept in an era where edible protein can be grown in a lab. But the need for healthy organs and blood has only increased. And so the farm has transformed from a place of pork to one of kidneys, hemoglobin, and new life.
The Natural Chimera
The chimera is a Greek mythological monster said to have the heads (and other body parts) of a goat, a lion, and a dragon. In Homer’s Iliad, she is slain by the hero Bellerophon while he is astride the winged horse Pegasus, an event immortalized in pottery and mosaic across the Mediterranean. In modern times, the chimera has lent her name to a scientific phenomenon known as chimerism, in which two zygotes fuse during development to create a single organism with two distinct genotypes.
Human chimerism is an extremely rare condition. Though it may manifest as having two skin-tones, multiple distinct blood types, mismatched eyes, or intersex characteristics, there are also instances where it may never be noticed without specific testing. The most famous instance of this is the case of Lydia Fairchild, who was accused of welfare fraud after a maternity test revealed that, somehow, her two biological children were not genetically related to her. After an extended legal battle and medical testing, it was finally revealed that Lydia was “tetragametic”— she was the fusion of two fertilized zygotes in the womb. Her ovaries carried the genetic code of her “fraternal twin”, and so her eggs (and children) did not register as being genetically descended from the rest of her body. This case was fundamental to changing how science understood chimeras, which were formerly thought to be equal distributions of both halves across the individual. Instead, we now know that many chimeras only exhibit distinct DNA in specific, often microscopic, areas of their bodies, which raises many questions for how legal and medical care may often overlook those who unknowingly have this condition.
The Myths We Make
The chimera is a rare and wonderful creature, uniquely valuable for research and strange in its development. Methods of developing mouse chimeras have been employed for several decades in labs. Combining zygotes at different stages of development have taught researchers how cells “decide” which DNA contributes to which system in the body and the role of genetic diversity within a single individual on disease progression and recovery. Chimeric cells can even be used in a medical application: injection of pluripotent, chimerically-created cells into the tissues of mice showed promising rates of wound regeneration and repair. Adult chimeras were also better suited to tissue homeostasis, and could “compensate” for genetic deficiencies, such as failure to make a particular protein, by allocating production to the functional, unmutated DNA. Mice were even able to survive when combined with rat DNA; in many specimens, the blastocyst was able to incorporate usable pieces of the rat’s genetic code while excising pieces that would lead to fatal deformities— such as the growth of a gallbladder, which is an organ possessed by rats but not mice.
Beyond its success as a novelty, the mouse-rat chimeras raise another question: is there a future for human hybrids, mingling Homo sapien genetic material with other animals? The concept may seem like pure fantasy, but it has actually already happened in labs around the world. The realm of genetic combination is rife with moral questions, strange creations, and the potential for life-saving medical advancement.
Miracle Working
“Human hybrid”, though not semantically incorrect to say and fun to imagine, is a misleading name for the sort of chimeras being used in modern research. There are no people being grown to have mouse organs or one-of-a-kind physical mutations like Lydia Fairchild. Instead, human DNA is being specifically introduced to animal hosts. The results are animals that develop with some variety of human cells, but rarely have obvious physical deformities. The first ever of these hybrids, which combined human and rabbit DNA, never matured beyond the embryonic stage. However, modern chimeras with human cells can survive to adulthood.
Chimeras both fetal and grown— which are currently composed mainly of mice, pigs, and cows— have become invaluable in the medical field. This is because human-nonhuman chimeras with human tissues, blood, or organs act as substitutes for human beings when it comes to laboratory experimentation. At Stanford, human-cow chimeras can be used to monitor the viral progression of HIV, while pigs that manufacture human-like T-cells function as models of the human immune system. In the United Kingdom, chimeras are allowing scientists to study human-only diseases such as Down syndrome. Mice exhibiting “behaviors, organ size, and neuronal numbers that mimic the human disease” are used to study the onset and differentiation of adverse effects.
In addition to the study of diseases, chimeras are involved in making cures, too. Human-nonhuman organisms allow much more accurate testing of new drugs under FDA guidelines, which require extensive tests and trials before being released to the public. But trials on mice, though extremely valuable, are inherently limited by the physiological differences between rodents and humans. Engineering mice with human cells in place of the organ or system targeted by a new drug, however, gives researchers more accurate results. This not only reduces the wait between the inception of a potentially life-saving medicine and its approval by the FDA, but also lowers the risk of adverse side-effects when moved to a purely human trial. The final modern use for chimeras is both the most advanced and most controversial: xenotransplantation. The FDA defines xenotransplantation as “any procedure that involves the transplantation, implantation or infusion into a human recipient of […] live cells, tissues, or organs from a nonhuman animal source”. One form of this is already widely used: fish skin grafts for burn wounds. Fish skin has been proven to reduce inflammation and promote wound healing, making it a relatively low cost but highly effective resource used by many hospitals. The other major form of xenotransplantation is much less common: organ transfer from animals to people. In response to the organ-donor crisis, wherein sixteen people die every day from unavailability of life-saving organs, scientists have turned to chimeras to provide human organs for those in need. In March, 2024, the first pig kidney was successfully transplanted into a patient in dire need. Over sixty-nine genomic edits were done to the kidney, including the addition of several human genes to create a chimeric organ. Though the long term effects of living with a transplanted porcine kidney are unknown, the patient successfully produced urine and was discharged in a healthy state a week later. The team behind this transplant say that the pig kidney is only intended as a temporary measure— expected to last a year or two— but hope that this will give their patient enough time to find a human donor.
Of course, this was merely the first success in what will hopefully become a staple solution for many sick people in need of organs beyond just kidneys, but hearts, livers, and pancreatic islets, as well. Especially with the increasing success in producing fully human organs or gametes in animal hosts, chimeras may someday become a source of permanent organ donation.
Respecting the Resource
Chimeras have the potential to save many lives and reveal scientific mysteries. In many cases, they are never grown past the embryonic stage, when they are little more than clumps of genetically altered or combined cells. However, for use in drug trials or organ donation, full, living chimeras are reared, creatures which usually look no different from typical farm animals. Already, there exist several farms that raise pigs for the express purpose of research into xenotransplantation, leading to concerns over the treatment of these animals. David Ayares, head of a biotech company known as Revivicor which runs one of these pig-editing facilities, acknowledges these concerns. However, he and his team believe they are raising their animals for a “higher purpose”— saving lives— than other pig farms, which almost exclusively operate for meat production. Additionally, the Revivicor farm and laboratory only raises several hundred pigs at a time, giving them room to roam, toys to play with, and quality medical care. In some ways, life as a potential organ donor is more humane for pigs than life in a corporate pork farm, which are often overcrowded, cruel, and painful for the sake of profit. Of course, were the demand for pig-grown organs to suddenly boom, organ-forms may face the same dilemma of growing beyond capacity in order to meet demand. This is not only inhumane for the animals, but also increases the risks associated with xenotransplantation.
This is directly related to another major concern with harvesting pig-grown organs: disease. If pigs are not properly raised, unexpected mutations occur, or there is carelessness in the transplant process, the risk of zoonotic illness transfer greatly increases. Even diseases that have yet to spread from animals to humans (such as the bird flu) are more likely to “make the jump” when implanted directly in the body. When the currently well-managed and small-scale genetic editing of chimeric pigs becomes a public good, the likelihood of cut corners or improper care could turn organ donation deadly. It will require strict regulations and oversight before broad-scale organ production can ever occur on a national or global scale. There are also concerns among religious organizations over the potential implications of receiving a pig organ. There is no agreed-upon consensus among Jewish or Muslim community leaders (faiths in which consuming pork is forbidden) over whether it would be a religious violation to receive an organ harvested from a pig. Some say that because the preservation of human life is paramount, animal material that is otherwise banned becomes permissible when the alternative would be potential death while on the transplant list. Others insist that pork-grown organs are fundamentally unclean. This community divide reminds us that transparency in the process of organ transplantation will be especially important should pig donors become more common, allowing every person to make an informed choice about the source of the organ they may be receiving.
What Makes Us Human?
There is no one universal answer to what makes us human. In some areas of science, particularly those that involve human lives or genes, the line between ethical conduct and cruelty can be difficult to see, especially when we lack information of the long term effects of experimentation. A rat whose brain was replaced with human neurons can never “think like a human”— their brain is too small to attain our level of cognitive function— but it technically does have a “human brain”. Could a conscious being be created if the same technique was done to a larger, more intelligent animal, like a pig or a primate? If two mice that were made to produce human gametes should mate, is their offspring… human?
These are the questions that scientists have no answer for. But they’re also likely never going to come to pass. Laws and guidelines surround the chimera-making process, ensuring nothing resembling a true human capable of higher reasoning is created. For instance, human material is only ever added to an animal embryo, never the other way around. Studies have shown that human cells do not compete well against native cells, making it unlikely that human genes could ever “take over” a host. There are also rules prohibiting the breeding of chimeras together, and upper limits on how many genes in a host can be replaced (for pigs, it is below 1%) to prevent development of potentially human-like features. None of these precautions completely eliminate ethical quandaries from the topic of chimeras, but they do serve to reinforce the barrier between human and animal so that all are treated with the proper respect and care.