Editor’s Corner
The Color of Blood and “Exohematology”
S
The content of the Editor’s Corner is
the opinion of the author and does
not represent the official position of
the American Society of Hematology
unless so stated.
PILLED BLOOD’S BRILLIANT RED color has
a rich symbolic history. The crimson color
chemistry of porphyrin-bound iron ions
led our ancestors to equate red with life
and vitality – and with danger and murder,
too. It is no accident that the reddest planet
in our solar system, Mars, is named after
the Roman god of war. From the ochre
rock painting of prehistoric Australia and
the famed Lascaux Cave, to Lady Macbeth’s
unwashable hands, Stephen King’s deeply
disturbing Carrie, and (spoiler alert!) the
tragic origin story of the eponymous fiddle
in The Red Violin, scarlet hues have long
been used by artists to signify shed blood.
But what if blood weren’t red? There is
no biological reason that our blood needs
to be that color, no specific physiologic
problem for which evolving liquid with a
ruby tint, instead of emerald or amethyst,
is the best possible solution. It is merely a
physicochemical accident. How might art,
literature, history, and religion be different
if, instead, human blood were the color of
the sky, the sea, or the Sahara?
Recent advances in astronomy – espe-
cially the discovery of water on Mars, and
detection of an abundance of Earth-like
exoplanets – increase the likelihood that
there is life elsewhere in the universe.
NASA now estimates that, in our galaxy
alone, there are at least a billion rocky,
Earth-sized planets orbiting yellow-orange
G-class stars like our Sun within a “habit-
able zone.” If we humans don’t annihilate
ourselves through anthropogenic climate
change, zombie apocalypse, or nuclear war,
we may someday discover strange new or-
ganisms that circulate an entirely different
liquid from what we know on Earth. If we
ever do find a creature on another world
with a substance resembling blood, will it,
too, be red?
In the meantime, as we wait patiently
for extraterrestrial contact and the
remarkable scientific discoveries that
would result, we can learn about some
of the possibilities for alien blood by
observing the diversity of creatures right
here on our home planet. Almost all
vertebrates have hemoglobin-containing
blood, yet there are plenty of terrestrial
precedents for non-red circulatory fluid.
The aptly named green-blooded skink of
New Guinea is one such variant: It has
hemoglobin, yet its blood and muscles
are lime-colored, due to enormously
high concentrations of biliverdin. (The
function of this high biliverdin level, le-
thal to non-skinks, is unknown.) Human
blood also occasionally takes on shades
other than red, such as the greenish tinge
of sulfhemoglobin or the chocolate-
brown hue of methemoglobin.
It is a common misconception, re-
inforced by schematic diagrams in text-
books like Frank Netter’s Atlas of Human
Anatomy, that human venous blood is
blue. Even in hypoxic conditions when
venous blood is almost black, it still re-
tains a mahogany tint. The more socially
pernicious concept of elite “blue blood”
originated with the Spanish sangre azul,
a medieval term used by leading Iberian
families to underscore their nobility. But
this descriptor was really about melanin,
not hemoglobin. Rich, pale-skinned
Spaniards would point to the veins on
their forearms to highlight that they
were not descended from darker-skinned
Moors; because they did not need to
work outside, they were not tanned. In
fact, human “blue blood” is a result of
light scatter from the walls of deep blood
vessels, not the blood within the vessels.
An octopus, in contrast, has genuinely
blue blood. The octopus uses hemocyanin
as a respiratory pigment. Hemocyanin is a
copper-containing cell-free substance that
is a brilliant sapphire when oxygenated and
nearly colorless when deoxygenated. Its
relative inefficiency as an oxygen trans-
porter compared with hemoglobin has not
prevented its use by other mollusks and
arthropods. Insects, spiders, lobsters, and
lower arthropods with an open circula-
tory system also have hemocyanin in their
blood equivalent, hemolymph, but they
don’t seem to use it for oxygen transport.
The sea squirt and a few related ma-
rine organisms have yet another kind of
pigment in their “blood”: vanabin, a
vanadium-binding metalloprotein that
can be green, blue, or orange and circu-
lates in a cell called a vanadocyte. Older
reports suggested that this vanadium
chromagen reversibly transports oxygen
like hemoglobin and hemocyanin, but
more recent studies have clarified that
hemovanadin is not actually a respiratory
The truth is out there: Dr. Steensma with the March
2019 issue of National Geographic and its very
timely cover story, “We Are Not Alone.”
pigment, and its precise function remains
mysterious even to senior “squirtologists.”
Curiously, the squirt’s heart flips the direc-
tion in which it squirts “blood” every few
minutes – almost as often as the weather
changes in New England or the Cleveland
Browns sign a new quarterback.
The sea squirt also reminds us that
an element need not be abundant in the
environment to be used by an organ-
ism. Hematologists knew this already,
given how common iron deficiency is
in the population and iron’s rarity in the
Earth’s crust. Vanadium ranks 31st in the
abundance list of elements found in the
oceans, averaging less than 1 part per
billion in sea water, yet the squirt and its
relatives can concentrate it more than
100-fold to make vanabin. Whatever
vanadocytes do for the squirt must be
important.
There is other odd blood underwater,
too. Leonard Zon, MD, at Boston Chil-
dren’s Hospital, bestows wine-inspired
names on the pale strains of mutant
zebrafish his lab uses to study hema-
topoiesis, including shiraz, Sauternes,
Chianti, and zinfandel. The anemia of
Have a comment about this editorial?
Let us know what you think; we
welcome your feedback. Email the
editor at [email protected].
6
ASH Clinical News
April 2019