Most animals with a backbone do have red blood, but the animal kingdom as a whole runs on a surprisingly wide palette. Octopuses bleed blue, certain marine worms bleed green or violet, a group of Antarctic fish bleed nearly colorless, and most insects do not use a dedicated oxygen-carrying pigment at all. The color of an animal’s blood comes down to which metal sits at the heart of its oxygen-transport molecule, and evolution has settled on several different solutions to the same basic problem of moving oxygen from the environment into hungry tissues.
Why Most Vertebrate Blood Looks Red
The red color familiar from a scraped knee comes from hemoglobin, a protein packed inside red blood cells. Hemoglobin contains iron at its core, bound within a ring-shaped structure called a heme group. When oxygen enters the protein, it passes through a channel created by a specific part of the molecule, gets captured inside an internal cavity, and then bonds with the iron atom. That iron-oxygen bond is what absorbs light in a way that makes the protein appear red.
Oxygen-rich hemoglobin is bright crimson, while oxygen-depleted hemoglobin shifts toward a darker, more maroon shade. This is why blood drawn from a vein looks darker than blood from a cut on your finger. Despite a persistent myth, deoxygenated blood is never blue. Veins look bluish through the skin because of how light scatters through tissue, not because the blood inside them has changed color.
Hemoglobin is ancient. Phylogenetic studies show that globin genes trace back to duplication events that predate the split between two enormous branches of animal life, meaning the molecular ancestors of hemoglobin were around long before vertebrates existed.1Hemoglobin. Evolution of the vertebrate globin gene family It became the dominant oxygen carrier in vertebrates because it works well across a huge range of body sizes, metabolic rates, and environments. But hemoglobin is far from the only option evolution has produced.
Blue Blood in Octopuses, Crabs, and Spiders
Swap iron for copper and you get hemocyanin, the oxygen-transport protein responsible for blue blood. Hemocyanin is found in many mollusks and arthropods, including octopuses, squid, lobsters, crabs, and horseshoe crabs. Unlike hemoglobin, hemocyanin floats freely in the blood (called hemolymph in these animals) rather than being packed inside cells. Each hemocyanin molecule is enormous, built from many subunits that each contain a pair of copper atoms. When oxygen binds to that copper pair, the protein turns blue.2Journal of Molecular Biology. Crystal structure of a functional unit from Octopus hemocyanin
Copper-based oxygen transport has its own advantages. Hemocyanin tends to work well in cold, low-oxygen environments because it shows cooperative binding, meaning it becomes more efficient at grabbing oxygen under certain conditions. Research on the hemocyanin of a South American marine snail demonstrated this cooperative behavior and showed that its oxygen-binding characteristics shift with temperature.3Biochimica et Biophysica Acta (BBA) – Proteins and Proteomics. The oxygen-binding properties of hemocyanin from the mollusk Concholepas concholepas For a deep-sea octopus living in near-freezing water with limited dissolved oxygen, hemocyanin can be a better fit than hemoglobin would be.
Hemocyanin also pulls double duty. In horseshoe crabs, the same protein that carries oxygen plays a role in a remarkably sophisticated immune defense system. The hemolymph of the horseshoe crab contains just a single type of blood cell, the granular amebocyte, and only three major proteins in its plasma: hemocyanin, a C-reactive protein that destroys foreign cells including bacteria, and a protease inhibitor that blocks enzymes released by invading pathogens.4PubMed Central. Blood collection from the American horseshoe crab, Limulus polyphemus When bacteria breach the horseshoe crab’s defenses, its blood cells release an arsenal of clotting and antimicrobial proteins from specialized granules, forming a rapid seal and killing microbes at the wound site.5Cellular Microbiology. Biomolecules of the Horseshoe Crab’s Hemolymph: Components of an Ancient Defensive Mechanism and Its Impact on the Pharmaceutical and Biomedical Industry That clotting reaction is so sensitive to bacterial toxins that pharmaceutical companies have used horseshoe crab blood for decades to test whether medical devices and injectable drugs are free of contamination.
Green Blood From Different Sources
Green blood shows up in the animal kingdom through two completely unrelated mechanisms, and the distinction matters because one involves a different oxygen-carrier molecule and the other involves a pigment that has nothing to do with carrying oxygen at all.
Several families of polychaete worms (segmented marine worms) use a protein called chlorocruorin instead of hemoglobin. Chlorocruorin is iron-based, just like hemoglobin, but its heme group has a small chemical tweak: one of the side chains on the porphyrin ring is swapped out. That single substitution shifts the way the molecule absorbs light, turning the blood green. The protein is structurally elaborate, with small subunits grouped into increasingly larger assemblies that form massive particles.6PubMed. Ligand binding and slow structural changes in chlorocruorin from Spirographis spallanzanii Some worm species even carry both chlorocruorin and hemoglobin in their blood at the same time. The serpulid worm Serpula vermicularis, for example, has iron distributed across both pigments, with roughly 60% of its blood iron present as the chlorocruorin form and 40% as hemoglobin.7Comparative Biochemistry and Physiology Part B: Comparative Biochemistry. The respiratory pigment of the serpulid polychaete, Serpula vermicularis L. Structure of its chlorocruorin and hemoglobin (erythrocruorin)
The other kind of green blood turns up in a much more unexpected place: lizards. Several species of skinks in the genus Prasinohaema, found in New Guinea, have blood that looks vividly green even though they carry normal red blood cells with hemoglobin inside them. The green color comes from biliverdin, a bile pigment that is normally a waste product of hemoglobin breakdown. In these lizards, biliverdin accumulates in the plasma at concentrations so extreme that the green overwhelms the red, coloring not just the blood but also the muscles, bones, tongue, and mouth lining.8PubMed Central. Multiple origins of green blood in New Guinea lizards Measurements of biliverdin levels in three Prasinohaema species found concentrations ranging from roughly 700 to over 1,000 micromoles per liter, the highest plasma biliverdin levels ever recorded in any organism and the first known case of non-pathological biliverdin accumulation in a land vertebrate.9Comparative Biochemistry and Physiology Part A: Physiology. Green-blood pigmentation in lizards
In humans, elevated biliverdin would signal serious liver disease. These lizards thrive with it. Genetic analysis has shown that the green-blooded trait arose independently multiple times across different Prasinohaema lineages, suggesting it provides some real evolutionary advantage, though researchers are still debating what that advantage is. Hypotheses include protection against blood parasites like malaria, since biliverdin can be toxic to the parasites that infect red blood cells.10Journal of Heredity. The first de novo genome assembly and annotation of a green-blooded skink (Prasinohaema aff. flavipes) from a historic museum sample
Fish With Nearly Colorless Blood
If green-blooded lizards seem improbable, consider a group of fish that have abandoned hemoglobin entirely. The Antarctic icefishes, a family of about 16 species living in the frigid Southern Ocean, are the only known vertebrates whose adult blood carries no hemoglobin and no red blood cells. Their blood is pale, almost translucent.11Journal of Experimental Biology. When bad things happen to good fish: the loss of hemoglobin and myoglobin expression in Antarctic icefishes
This did not happen overnight. Genomic studies reveal that icefishes retain broken remnants of alpha-globin genes but appear to have lost the beta-globin gene entirely, either through deletion or rapid mutation, before the family diversified into multiple species.12PubMed. Genomic remnants of alpha-globin genes in the hemoglobinless antarctic icefishes More recent genomic analysis of eight icefish species confirms that both major hemoglobin gene clusters have been lost or gutted across the entire family.13PubMed Central. Cold-Driven Hemoglobin Evolution in Antarctic Notothenioid Fishes Prior to Hemoglobin Gene Loss in White-Blooded Icefishes
How do they survive? Cold water holds far more dissolved oxygen than warm water, and these fish have evolved compensatory traits: larger hearts, greater blood volume, wider blood vessels, and scaleless skin that absorbs oxygen directly. Some icefish species have also lost myoglobin, the oxygen-storage protein in muscle tissue, making their hearts look ghostly white rather than the usual pink. The result is a vertebrate that gets by on passive oxygen diffusion where most other fish would suffocate. It is a vivid illustration of how a trait that seems essential, like hemoglobin, can become dispensable when the environment changes enough.
Insects and the Animals That Skip a Respiratory Pigment
Most insects do not carry an oxygen-transport pigment in their blood at all. Instead of relying on their circulatory fluid to shuttle oxygen around, insects use a network of tiny air-filled tubes called tracheae that pipe oxygen directly from the atmosphere to their internal organs. Because the gas delivery is handled by this tracheal system, specialized oxygen-transport proteins in the blood have generally been considered unnecessary.14PubMed Central. A respiratory hemocyanin from an insect Insect hemolymph is often yellowish or greenish, colored by dietary pigments and metabolic byproducts rather than by any respiratory molecule.
There are exceptions. The larvae of chironomid midges, the small non-biting flies you might see swarming near lakes, produce hemoglobin and are bright red as a result. These larvae live buried in oxygen-poor sediment at the bottom of freshwater bodies, and their hemoglobin allows them to store and use oxygen in conditions that would suffocate other insects. This ability to thrive under extreme low-oxygen conditions has made chironomid larvae a useful model for studying environmental stress in freshwater ecosystems.15Journal of Limnology. Extracellular hemoglobin and environmental stress tolerance in Chironomus larvae The same source also found hemocyanin serving a respiratory function in a large stonefly, challenging the assumption that insects never need blood-borne oxygen carriers. These outliers tend to share a common thread: they live in low-oxygen environments where the tracheal system alone is not enough.
Tunicates and Their Vanadium Mystery
Sea squirts, formally known as tunicates, add yet another chemical twist. Some tunicate species accumulate vanadium in specialized blood cells called vanadocytes at concentrations millions of times higher than the surrounding seawater. For decades, scientists debated whether vanadium played a role in oxygen transport, but that hypothesis has never been convincingly supported. The blood cells themselves sit at a near-neutral internal pH, around 7.2 for vanadocytes, which argues against the highly acidic conditions that were once proposed as a feature of these cells.16PubMed. Vanadium-containing tunicate blood cells are not highly acidic
The actual function of vanadium accumulation remains one of the more persistent puzzles in marine biology. Proposed roles include defense against predators, antimicrobial activity, and structural functions in the animal’s tough outer tunic. What is clear is that tunicate blood does not fit neatly into the hemoglobin-versus-hemocyanin framework that describes most animal respiratory pigments. It is a reminder that “blood” does many things beyond carrying oxygen, and that not every blood pigment is a respiratory pigment.
Tubeworms at Hydrothermal Vents
Some of the most extreme oxygen-carrying demands in the animal kingdom belong to giant tubeworms that live near deep-sea hydrothermal vents. These worms, like Riftia pachyptila, have no mouth, no gut, and no ability to feed. Instead, they rely entirely on symbiotic bacteria housed in a specialized organ. The bacteria need both oxygen and hydrogen sulfide to produce energy through chemosynthesis, and the tubeworm’s hemoglobin has to deliver both substances simultaneously through the blood. This is a remarkable trick because in most animals, sulfide is highly toxic and would poison hemoglobin on contact.17Molecular Biology and Evolution. Evolution of the Sulfide-Binding Function Within the Globin Multigenic Family of the Deep-Sea Hydrothermal Vent Tubeworm Riftia pachyptila
Structural studies of vent tubeworm hemoglobin revealed that zinc ions in the protein play a key role in binding sulfide at a separate site from where oxygen attaches, keeping the two molecules apart so they do not interfere with each other.18PubMed Central. Sulfide binding is mediated by zinc ions discovered in the crystal structure of a hydrothermal vent tubeworm hemoglobin Other vent tubeworm species, like Ridgeia piscesae, adjust their hemoglobin gene expression depending on the local chemistry of the vent fluid, fine-tuning how much protein they produce to match the available oxygen and sulfide.19PubMed. Environmental differences in hemoglobin gene expression in the hydrothermal vent tubeworm, Ridgeia piscesae These worms have bright red blood, because their hemoglobin is still iron-based, but the molecule has been repurposed far beyond simple oxygen delivery.
Biliverdin Beyond Lizards
The green-blooded skinks of New Guinea are the most dramatic example of biliverdin coloring an animal’s blood, but they are not the only case. Elevated biliverdin has also been reported in the blood plasma of certain marine fish, where it gives the plasma a blue-green tint. Research has documented biliverdin, bound to protein, as the pigment responsible for this coloration in several fish species, and the pigment also shows up in the blood of some frogs, in the wings of moths and butterflies, and in eggshells of certain birds. In most of these cases the biliverdin concentration is far lower than in Prasinohaema, and it does not appear to serve a respiratory function. The widespread occurrence across distantly related animals suggests biliverdin is biochemically easy to retain or repurpose once it is produced as a byproduct of hemoglobin recycling. Whether it provides antioxidant protection, parasite defense, or camouflage likely varies from species to species.
Borrowing From Nature for Human Medicine
The diversity of blood pigments across the animal kingdom is not just a curiosity. Researchers have been studying the giant hemoglobin molecules found in certain invertebrates as potential alternatives to human blood transfusions. Conventional efforts to create artificial oxygen carriers based on mammalian hemoglobin have repeatedly run into problems with instability and toxicity. But erythrocruorins, the massive hemoglobin-like proteins found in earthworms, lugworms, and some crustaceans, may avoid those issues. Studies of erythrocruorins from the common earthworm and the lugworm Arenicola marina have shown that these molecules transport oxygen efficiently and even have anti-inflammatory properties.20PubMed Central. The artificial oxygen carrier erythrocruorin-characteristics and potential significance in medicine
The lugworm hemoglobin has progressed the furthest toward clinical use. A product called M101, derived from Arenicola marina hemoglobin, was tested in a first-in-human clinical trial as an additive to organ preservation solutions during kidney transplantation. The idea is that by supplying oxygen to the donated kidney during the hours it spends outside the body, the hemoglobin can reduce the damage caused by oxygen deprivation.21American Journal of Transplantation. First-in-human use of a marine oxygen carrier (M101) for organ preservation: A safety and proof-of-principle study A larger multicenter randomized trial, OxyOp2, has been designed to further evaluate whether this marine-derived hemoglobin can improve outcomes for transplant recipients.22PubMed Central. Evaluation of the efficacy of HEMO(2)life®, a marine OXYgen carrier for Organ Preservation (OxyOp2) in renal transplantation: study protocol for a multicenter randomized trial A molecule that evolved in a burrowing beach worm to survive low-oxygen tidal flats might end up saving kidneys in operating rooms. Evolution’s experiments with blood chemistry, it turns out, are also a parts catalog for biomedical engineering.