You Make the Call:
Readers’ Response
these fish make their blood hue fall short
of the darker color of vintage Burgundy
or of Brunello di Montalcino.
While Dr. Zon’s fish are genetically
engineered artificial human creations,
the ocellated Antarctic icefish, a scaleless
organism that has clear-colored blood
lacking both hemoglobin and hemo-
cyanin, evolved naturally. As the icefish
lives only in frigid parts of the Southern
Ocean, and cold water can hold a higher
dissolved concentration of oxygen than
warm, icefish apparently get enough
oxygen by simple diffusion – common
among small insects, but incredibly rare
for a vertebrate. Whether icefish blood
also is “thicker than water” is something
one would need to interview a variety of
extended icefish families to confirm.
Transitional metals in the d-block
of the periodic table have the optimal
atomic properties for reversible oxygen
binding, and also tend to have a particu-
larly vibrant color palette. It is possible to
imagine organisms that might use cobalt,
iridium, or manganese instead of iron
or copper as a reversible oxygen trans-
porter. Chemists tell us that coboglobin
would be light pink if oxygenated and
amber-yellow if deoxygenated, while a
manganese metalloprotein is likely to be
pink, purple, or brown. There’s a prec-
edent for a cobalt-containing porphyrin
pigment: We call it vitamin B 12 .
Speculative fiction often explores
non-human biological possibilities,
including alien hematology. Star Trek’s
Mr. Spock famously had green blood,
allegedly because the Vulcan oxygen-
containing pigment is, like that of the
octopus, copper-based. Star Trek’s
writers were likely more familiar with
how copper roofing material oxidizes to
green than they were with blue-blooded
terrestrial arthropods. Since Spock
was half-human, we must assume the
green gene is dominant over red, unless
his stem cells are chimeric and green
hematopoiesis dominates. Incidentally,
Vulcan “green cells” – we can’t call them
erythrocytes or red cells – are lentil-
shaped rather than biconcave. Ash, the
nearly immortal android in 1979’s creepy
Alien, “bled” a sticky white goo. Video
game and anime characters often spray
pixelated orange, yellow, black, or purple
liquids when injured, just to emphasize
how weird they are.
A few years ago, I rewatched
Spielberg’s E.T. the Extra-Terrestrial with
my daughters. There is a bizarre moment
in the resuscitation scene near the end
of the movie – a scene that terrified me
at age 11 and also brought tears to the
eyes of my then-similarly-aged girls. Just
before E.T. is given an injection of brety-
lium (!) and defibrillation is attempted, a
scientist working on an oscilloscope-like
green monochrome instrument in the
background of the isolation tent announc-
es that E.T.’s DNA has six different base
pairs instead of four. How it was possible
to discover this basic biology fact in the
midst of a code – in 1982, no less – is left
unexplained. Nor is there any discussion
of why E.T.’s species would need to be able
to encode at least 215 amino acids (i.e., 63
minus a stop, if his cells used three-base
codons), a critical biological question per-
haps edited out to make room for Reese’s
Pieces product placement.
Some years ago, I attended a NASA-
sponsored conference on astrobiology in
Washington, DC. Astrobiology, some-
times called exobiology, is an evolving
interdisciplinary field that focuses on
the origin, distribution, and future of
life, wherever it might be found in the
universe. I had a wonderful time at the
meeting, in part because it was so inter-
esting scientifically and in part because it
can be fascinating to walk into someone
else’s world for a while and just listen and
learn. Instead of the presentations on
sickle cell disease or leukemia I was used
to, the astrobiology conference’s plenary
session featured talks about the design
of interplanetary probes and some new
discoveries in archaebacteria genom-
ics. There was even a keynote lecture by
Harrison Schmitt, the most recent hu-
man to have walked on the moon (Apollo
17, December 1972).
As always with space exploration,
questions were raised at the conference
about whether such costly, high-risk
science and engineering is justifiable in
a world with entrenched poverty and so
many social ills. A reader of this essay
might ask a parallel question about wheth-
er it is worth devoting space in an ASH
publication to exploring the possible con-
figurations of extraterrestrial blood. It is
a fair question, but, at some level, science
is its own reward. And comparison with
different possibilities can make us think
differently about our own blood, begin-
ning with its color, and imagine how it
might have been otherwise.
TRAIN ING
We asked, and you answered! Here are a few
responses from this month’s “You Make the
Call.”
TION
and EDUCA
ue program
Consult a Colleag ’s clinical
through the
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This month
You Make
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for at least
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seek consult
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qualified experts
For the full description of the clinical dilemma,
and to see how the expert responded, turn to
page 29.
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• Anemia
poietic cell
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Expert Op
MD
Marilyn Telen,
Medicine
Professor of
Wellcome
Center
Hematology
Sickle Cell
Division of
Comprehensive
Director, Duke Medical Center
ity
Duke Univers
of signs
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* If you have
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ER: ASH
DISCLAIM
I have a 42-year-old female patient who has
had very low B 12 levels for at least a decade.
This is the first time she has seen a hematolo-
gist. She does not have persistent anemia,
red cell macrocytosis, or neurologic symptoms. Her methylmalonic acid levels and
B 12 -binding capacity have been normal. She has had a lot of gastrointestinal issues
and, at various times, small bowel Crohn disease as well as small intestine bacterial
overgrowth, which have required therapy. At this time, she is not on any treatment
other than dietary restrictions and desipramine.
She does not tolerate parenteral, oral, or nasal supplementation so stopped
them. As far as she knows, there is no family history of B 12 issues. My best guess is
that she has some form of B 12 -binding protein abnormality that is not of any func-
tional consequence. I tried to find a way to assay for transcobalamin 1 but have not
had success. Any suggestions regarding further testing, if needed, or management
are welcomed.
ASH Clinical
News
29
org
ASHClinicalNews.
Measure holotranscobalamin levels.
A. Saifudeen, MBBS, MD, FRCP
Salalah, Oman
Thank you for posting this difficult clinical
scenario of a patient with Crohn disease
and low B 12 levels.
Given her normal methylmalonic acid
levels and no manifestation of B 12 I feel
somewhat reassured.
Have you tried sublingual B 12 or B 12
patches?
Satvir Singh, MD
Snellville, GA
Back to basics: Treat the patient, not the
tests.
Catherine Cole, MBBS, FRACP, FRCPA
Dohar, Qatar
Have you done the old time-honored
Schilling test? If that is normal, I would
not do any B 12 quantitation, as long as
she is asymptomatic.
Susumu Inoue, MD
Flint, MI
David Steensma, MD
Have you tried sublingual B 12 supplements?
This patient obviously has low/very-low
vitamin B 12 levels for many years with-
out any symptoms suggesting a vitamin
B 12 deficiency (neither any hematologic
nor neurologic symptomatology). This
is compatible with haptocorrin defi-
ciency. Haptocorrin (previously denoted
transcobalamin I and III) carry about 70
to 90 percent of the total vitamin B 12 in
serum, however this part of vitamin B 12
is not available for most cells, such as
erythroid precursors. Only vitamin B 12
bound to transcobalamin (previously
denoted transcobalamin II) is available
for most cells, such as hematopoietic
precursors. This transcobalamin-bound
vitamin B 12 is therefore considered to be
the “active vitamin B 12 ” and constitutes
only 10 to 30 percent of the total mea-
sured vitamin B 12 .
This patient, therefore, probably
has normal active vitamin B 12 ; this could
be confirmed by measuring specifically
holotranscobalamin. The low vitamin
B 12 level is likely caused by low holohap-
tocorrin (i.e., the vitamin B 12 bound to
haptocorrin).
No treatment will be needed in this
woman.
Bernhard Lämmle, MD
Mainz, Germany
Daniel O. Cuscela, DO
West Palm Beach, FL
See more reader responses at ashclinicalnews.org/
category/training-education/you-make-the-call.
ASHClinicalNews.org
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