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in time for the final episode. In 1959 the British Medical Journal reported on something
that had never been seen before - several patients with a mysterious condition, something happening
inside their blood that doctors didn't think was possible. Historically, we've understood
our blood types to be a constant immovable fact of our genetics and of our existence.
But what these doctors found were several definitive cases of people with an A blood
type showing signs of their blood type changing suddenly having red blood cells temporarily
expressing the B blood type antigen. This acquired B phenomenon, as it's called,
was never seen in healthy people, only ever in people with cancer in their stomach or intestine
or with some other condition where the integrity of the gastrointestinal wall was compromised.
Over time their blood type would return to normal, but scientists were not entirely sure
what had caused it. In 1972 detectives found a dismembered body in the River Thames. During
the forensic investigation one body part recovered was shown to have O type blood. Later, however, a
different part that had remained in the water for a longer period was identified as having B-type
blood. The blood groups therefore implied the two parts were not from the same individual. However
other evidence determined beyond a shadow of a doubt that the two parts did belong to each other.
This therefore raised the suspicion that the second part found had an acquired B-type blood.
What is the common link in these two strange situations? It's not a change in genetics that's
causing the blood type to change, nor is it an accidental introduction of a different blood type
from somewhere else. It's the work of bacteria -specifically a certain type of bacterial enzyme
that cleaves or alters certain blood antigens turning one blood type into another. For the
first time scientists realized that our blood types are not so immovable after all. This
acquired B phenomenon can certainly raise problems with typing blood for medicine or with forensic
science, but it could also hold the answer to a very big problem. If blood can accidentally
be transformed from one type to another, can it be done on purpose? Can we use this idea to
change blood types in order to create universal donor blood that is always so desperately needed?
Every two seconds someone in the U.S. needs blood, but only around 38 percent of the U.S. population
is eligible to give blood or platelets. And less than ten percent actually do it. And only
seven percent of the population has the so-called universal donor blood O negative. The red cross
reports that on average it only has about six units of type O blood available for every one
hundred thousand people. But more than twice that is needed every day. You can start to see
the problem here. There is an ever-present need for blood, especially universal donor blood,
and only so much available. In a previous video I discussed the importance of the different blood
groups and the ABO and Rh systems. The ABO system is the most important and your group is determined
by the presence of the antigens A and B which are carried on the surface of your red blood cells.
You can have type A, B, AB, or O - O meaning you have neither of the A or B antigens. The ABO group
antigens are sugars that work to recognize foreign cells in the bloodstream. The O blood type lacks
the A or B antigen and only has what is known as the H antigen. It's sort of like a blank or base
antigen. the A and B antigens are then attached to this H antigen in the A and B blood types, and the
only difference between the A and B blood antigens is a single sugar at the end of each structure.
People with the A antigen on the surface of their red blood cells will have an antibody
against the B antigen found on the B type blood cells. And conversely people with the B antigen
will have antibodies against the a antigens found on A type blood. During transfusion if the wrong
type of blood is injected the red blood cells in the injected blood will be attacked by the
antibodies and the recipient's blood causing them to clump together or agglutinate this will result
in hemolysis or destruction of the red blood cells which causes serious illness and can be fatal for
the recipient the rh or rhesus system works in a similar way if you're missing the most important
rh antigens you're considered to have a negative blood type rh negative recipients can only receive
rh negative blood but rh positive recipients can receive either rh positive or negative blood
and this is how the eight most common blood types are formed and because the o negative blood type
does not produce an incompatibility reaction in any of the eight types it's considered to
be the universal donor it's extremely valuable in medical situations because in a sudden accident
there may not be time to assess a patient's blood for its type as they're bleeding out if in doubt
o negative blood will pretty much always be a safe bet but o negative blood can be very hard to come
by some solutions to the blood shortage aim to get more people to donate others aim to improve
the logistics of blood delivery helping to get it to the people who need it most but even if more
people donated the treadmill of supply and demand is still profoundly difficult to stay on top of
and this is why the idea of creating universal blood has floated around the scientific community
for decades if we could turn any type of blood into oh blood then many complications in the
blood donation network could be alleviated but how far are we from it becoming a reality
in 1982 scientists first experimented with the idea of turning any of the [ __ ] blood types
a b or a b into o blood because the a and b blood types differ from the o type in a simple
sugar chain scientists believed that they could convert a b and a b red blood cells to o type red
blood cells by removing these extra sugars with an appropriate enzyme such converted o red blood
cells could then in theory be used as universal donor blood this procedure wouldn't affect the
rh status of the blood however but conversion of a positive and b positive red blood cells
would yield o positive blood whereas a negative and b negative red blood cells would yield o
negative blood at the time of this experiment there was only one commercially available enzyme
that might be able to cleave these sugars alpha galactosidase derived from green coffee beans
this looked promising to researchers but the enzyme came with several problems
it required a low ph of 5.7 to do the conversion which is not ideal for red
blood cells that prefer a ph of around 7.4 and to do it a huge amount of enzyme was required
making the process inefficient and not economical and most significantly it could only cleave the b
type antigen not the a this is because this enzyme can cleave the galactose of the b antigen
but does nothing to the n acetyl galactosamine of the a antigen nonetheless scientists were
able to convert b-type blood to o blood which was a huge milestone these converted blood
cells were shown to have a normal lifespan and to be well tolerated in the human body
but because only 10 percent of the population has b-type blood versus the 46 of the population
that has a type including the a antigen this idea would not be viable until scientists could find an
a cleaving enzyme therefore little more was heard of this technology for many years
that is until 2007 determined to find the missing piece of the puzzle scientists began the hunt for
a brand new enzyme and they began to look in the place where the reports about the acquired
b phenomenon had first alluded to the world of microbes if gut or river bacteria could
accidentally transform blood types maybe the right enzyme could be found among the millions
of microbes that live there thus researchers began digging through 2 500 fungal and bacterial samples
looking for an enzyme that could efficiently cleave both a and b sugar groups and within these
samples of bacteria an answer was indeed waiting for them they discovered two new enzymes within
two different bacteria one often found in bodies of water and one found in the human gut the enzyme
found in the gut bacteria could cleave the b sugar group at a ph of seven and the enzyme found in
the river bacteria could cleave the a sugar group after a 60 minute incubation with the appropriate
enzyme red blood cells with a b and a b antigens no longer expressed any of them they had all been
converted to the universal donor blood this looked like the answer that researchers had been looking
for for years but today this technology is still not in use something about this process was still
preventing it from moving into clinical practice although the enzyme found in river bacteria could
indeed cleave the a antigen it was still wildly inefficient the a cleaving enzyme was 30 times
less efficient than the bee cleaving enzyme 60 milligrams of enzyme per unit of red blood cells
was needed to convert a to o whereas only two milligrams of enzyme was needed to convert b to
o and this is not a trivial difference isolation and purification of enzymes is a costly process
enzymes need to be optimized for stability and efficiency expressed in some unlucky organism in a
massive fermenter purified to an insane degree and then packaged handled and shipped and if the idea
is to convert all blood types to oh blood even in remote parts of the world the cost of needing huge
amounts of enzyme would make the whole thing infeasible the dream of creating a universal
blood was once again tabled but 16 years later scientists have become armed with new technology
metagenomic analysis historically to search for new enzymes researchers would have to collect
samples of microbes from the environment and then culture them a method of multiplying the organisms
by letting them reproduce in the lab this of course takes a fair amount of time and effort but
with metagenomic analysis scientists can assess the genetics of everything in a sample at once
and look for the desired genes because of this researchers were able to screen 20 000 bacterial
samples from the human gut looking for an enzyme that could efficiently cleave the a antigen
at first they didn't see anything promising but when they tested two of the resulting enzymes at
once the a antigen came right off the two enzymes are a type of deacetylase and galactoseminidase
and are from a bacteria called flavonofractor plowtai when they work together they provide
the solution that has eluded scientists for years and only tiny amounts are needed as little as one
milligram per unit of red blood cells versus the 60 that was needed in previous studies
their high efficiency means they could be cost effectively added to the already existing routines
of blood collection processing and storage with major implications for the global blood supply
typing blood could become obsolete and everyone who donates could become a universal donor
people with the more rare blood types won't have to wonder if the right blood will be available
to them and countless lives could be saved this breakthrough paper was only published last year
so time will tell how soon we can see this in the real world but there's a lot of reason to
be optimistic for now though more work is needed to ensure that all of the a antigens
are thoroughly removed and that the process will not cause any adverse effects in the recipient
and researchers also need to make sure the microbial enzymes have not inadvertently altered
anything else on the red blood cell that could cause problems but it looks like this decades-long
quest may be over and that the reality of oh blood synthesis is right around the corner
the blood supply chain is a complicated ever-moving machine it's a global treadmill
that thousands work tirelessly to stay on top of and never is that supply chain more
important than in times of war and examples from the 20th century show us exactly how true that is
during world war ii the american red cross flew almost 200 000 pints of whole blood from the
us to the allied forces in europe more than 50 000 pints of blood were needed for the soldiers
fighting during the d-day invasion of normandy alone and coordinating this was not a trivial task
as germany tried to conquer the continent of europe the allied forces became locked in a war of
force and power yes but also one of supply chain logistics and during the invasion of normandy
this contest came to its most important climax years of planning hundreds of thousands of men
thousands of ships tanks and trucks hundreds of gliders and airborne troops all working together
to pull off the largest amphibious invasion in military history an invasion that would change
the course of history forever if you're interested in how the allies were able to coordinate such a
massive military effort then you should catch up on the logistics of d-day series made by
our other channel real engineering available exclusively on nebula it's a multi-part series
with episodes about the logistics of close air support fuel supply deception tactics and more
the final episode in the series will be released soon detailing the famed truck convoy the red
ball express that supplied allied forces moving quickly through europe after breaking out from the
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