Pig blood is the closest match to human blood among all animals studied, both in hemoglobin structure and red blood cell properties. This similarity has made pigs the leading candidate for cross-species blood products and organ transplants. But the answer gets more interesting when you look at why pig blood is so similar, what still makes it incompatible without modification, and how other animals compare.
Why Pig Blood Leads the Pack
Researchers investigating artificial red blood cells have mapped the structure of pig hemoglobin (the protein that carries oxygen in blood) at high resolution and directly compared it to the human version. The two are remarkably alike in three-dimensional shape, and the surface electrical charges on pig hemoglobin closely complement the surrounding cell membrane in ways that mirror human biology. This structural similarity is why pig hemoglobin has been seriously explored as a foundation for synthetic human blood products.
Beyond hemoglobin, pig blood shares other practical similarities with ours. Pig red blood cells are close in size to human red blood cells, and the oxygen-carrying behavior is comparable. Pigs are also large enough to produce meaningful volumes of blood, which matters for any medical application. These factors together explain why, when scientists talk about animal-to-human blood compatibility, pigs come up first.
The Immune Barrier That Still Exists
Similar doesn’t mean identical. If you transfused unmodified pig blood into a human, the immune system would attack it within minutes. The culprit is a sugar molecule called alpha-Gal that sits on the surface of pig blood cells and blood vessel walls. Humans lost the ability to produce this sugar during evolution, so our immune systems treat it as a foreign invader. The reaction is violent and fast, causing the transfused cells to clump and break apart.
Gene editing has changed the equation. Scientists can now knock out the gene responsible for producing alpha-Gal in pigs, creating animals whose tissues no longer trigger that immediate immune response. In 2020, the FDA approved these modified pigs, known as GalSafe pigs, for therapeutic use including transplantation research. This was a landmark step, and it opened the door to clinical trials now underway.
Cow Blood in Medical Products
Cows deserve a mention here because their hemoglobin has actually been processed into a product called Hemopure, a hemoglobin-based oxygen carrier designed to substitute for human blood in emergencies. Unlike a true blood transfusion, Hemopure strips hemoglobin from cow red blood cells and chemically stabilizes it so it can carry oxygen through the human bloodstream without the cell surface markers that would trigger rejection.
The concept works in principle, and Hemopure has been tested in human patients. However, regulatory approval has been blocked in most countries due to concerns about serious side effects, including an increased risk of heart attacks observed in clinical trials. South Africa approved it for limited use, but it remains unavailable in the United States and Europe. So while cow hemoglobin can technically deliver oxygen in a human body, the safety profile has kept it off the market for decades.
Where Primates and Sheep Fit In
You might expect that primates, our closest genetic relatives, would have the most compatible blood. Rhesus macaques are the reason we even use the term “Rh factor” in blood typing. But the relationship is more complicated than the name suggests. When researchers tested rhesus monkey blood for the standard human Rh antigens (C, D, E, and c), they couldn’t detect them using the same methods that work for human blood. The monkey version of the D antigen appears to exist but is either buried too deep within the cell or structured differently enough that it doesn’t react with human antibodies in a straightforward way. Monkeys and humans share a related antigen, but it’s not a clean match. Primate blood also comes with serious practical limitations: primates are small, slow to breed, and raise significant ethical concerns.
Sheep blood plays a surprising role in medicine, though not for transfusion. Laboratories around the world use sheep blood agar as the standard growth medium for culturing bacteria. Research comparing sheep blood agar to human blood agar found that human blood types A and O positive produced growth patterns most similar to sheep blood. For growing and isolating bacteria, sheep blood works well as a stand-in. But it falls short when labs need to observe hemolysis patterns (how bacteria break down red blood cells), because certain fastidious species like the pneumonia-causing bacterium S. pneumoniae behave differently on human versus sheep blood.
Early Attempts at Animal-to-Human Transfusion
The idea of using animal blood in humans is centuries old. In 1666, Richard Lower performed the first successful blood transfusion between two animals. The very next year, French physician Jean Baptiste Denis transfused blood from a lamb into a human patient. Lower himself then transfused lamb blood into an English clergyman named Arthur Coga. These early experiments didn’t end well. Without any understanding of blood types or immune rejection, the practice was abandoned for roughly 200 years. Safe human-to-human transfusion didn’t become possible until blood types and cross-matching were discovered in the early twentieth century.
Gene-Edited Pig Organs in Humans Today
The same blood compatibility research that identifies pigs as the closest match has driven a wave of real transplants. About half a dozen people in the United States and China have received organs from gene-edited pigs, including kidneys, hearts, a liver, and a thymus. These surgeries were performed on compassionate grounds for patients who had no other options.
The field is now moving into formal clinical trials. United Therapeutics is running a trial enrolling six people with end-stage kidney disease who are unlikely to receive a human donor kidney within five years. Patients will be monitored for six months for serious complications, then followed for life. A safety committee will review data from those first six patients before the trial potentially expands to 50 participants. Another company, eGenesis, received FDA approval in late 2024 to perform three pig kidney transplants under compassionate use and has applied to launch its own clinical trial. A team that performed the first pig heart transplant into a living person in 2022 is also pursuing FDA approval for heart transplant trials, though hearts present a harder regulatory path.
These trials rely on pigs with dozens of genetic modifications, not just the alpha-Gal knockout but edits targeting other sugar molecules and pig viruses embedded in the genome. The blood compatibility between pigs and humans is the biological foundation that makes all of this possible. No other animal offers the same combination of molecular similarity, body size, breeding efficiency, and genetic editability.